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Clinical Trial Results:
A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control

Summary
EudraCT number	2011-002528-42
Trial protocol	LV LT DE ES IT BG AT DK SE HU PL SK Outside EU/EEA GR FR
Global end of trial date	09 Oct 2019

Results information
Results version number	v1
This version publication date	24 Apr 2020
First version publication date	24 Apr 2020
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

0431-083

ISRCTN number

US NCT number

NCT01485614

WHO universal trial number (UTN)

Other trial identifiers

Merck Protocol Number: MK-0431-083

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000470-PIP01-08

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

09 Oct 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

09 Oct 2019

Global end of trial reached?

Yes

Global end of trial date

09 Oct 2019

Was the trial ended prematurely?

Main objective of the trial

The purpose of the study was to assess the effect of treatment with sitagliptin compared with placebo on glycated hemoglobin (A1C), and the safety and tolerability of sitagliptin, in pediatric participants (ages 10-17 years) with type 2 diabetes mellitus (T2DM) with inadequate glycemic control. The primary hypothesis for this study was that sitagliptin reduces A1C more than placebo after 20 weeks of treatment. Amendment 5 of the protocol removed 2 arms from the study (Metformin arm and the Placebo followed by Sitagliptin arm). Participants already in these 2 arms continued in the study. EUPASS4468 is a follow-up, observational assessment of safety of participants who participated in the MK-0431-083 study for up to 5 years.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measure defined for this study was in place for the protection of trial participants: glycemic rescue therapy, as appropriate, and as per the study glycemic rescue criteria, consisted of sitagliptin or metformin as an initial glycemic rescue (glycemic Rescue Step 1) and insulin as an additional glycemic rescue (glycemic Rescue Step 2), if needed.

Background therapy

Participants who were on insulin at screening continued receiving insulin during the study.

Evidence for comparator

Actual start date of recruitment

10 Feb 2012

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 1

Country: Number of subjects enrolled

Brazil: 1

Country: Number of subjects enrolled

Bulgaria: 6

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Colombia: 3

Country: Number of subjects enrolled

Costa Rica: 1

Country: Number of subjects enrolled

Dominican Republic: 12

Country: Number of subjects enrolled

Guatemala: 14

Country: Number of subjects enrolled

Honduras: 3

Country: Number of subjects enrolled

Hungary: 6

Country: Number of subjects enrolled

Israel: 19

Country: Number of subjects enrolled

Italy: 3

Country: Number of subjects enrolled

Latvia: 1

Country: Number of subjects enrolled

Lithuania: 1

Country: Number of subjects enrolled

Malaysia: 13

Country: Number of subjects enrolled

Mauritius: 8

Country: Number of subjects enrolled

Mexico: 23

Country: Number of subjects enrolled

Philippines: 8

Country: Number of subjects enrolled

Poland: 2

Country: Number of subjects enrolled

Romania: 2

Country: Number of subjects enrolled

Russian Federation: 30

Country: Number of subjects enrolled

Saudi Arabia: 7

Country: Number of subjects enrolled

Serbia: 2

Country: Number of subjects enrolled

Thailand: 3

Country: Number of subjects enrolled

United Arab Emirates: 2

Country: Number of subjects enrolled

United States: 28

Worldwide total number of subjects

200

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

175

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study recruited participants in clinics/clinical offices in 26 countries.

Screening details

The Pre-Assignment Period included a one-week single-blind placebo run-in prior to randomization during which participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Period 1 title

Randomization

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer

Are arms mutually exclusive

Yes

Sitagliptin

Arm description

In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Arm type

Experimental

Investigational medicinal product name

Sitagliptin

Investigational medicinal product code

Other name

MK-0431

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Sitagliptin treatment arm received one tablet of sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Placebo matching Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Placebo/Metformin

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo matching Sitagliptin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Placebo matching Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Metformin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Metformin

Arm description

In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, but ongoing participants in this arm continued in the same arm.

Arm type

Internal control

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Metformin treatment arm received two tablets of metformin prior to both the morning and evening meals (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).

Investigational medicinal product name

Placebo matching Sitagliptin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.

Placebo/Sitagliptin

Arm description

In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, but ongoing participants in this arm continued in the same arm.

Arm type

Placebo

Investigational medicinal product name

Placebo matching Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Investigational medicinal product name

Placebo matching Sitagliptin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Sitagliptin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.

Number of subjects in period 1	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Started	96	90	9	5
Completed	95	90	9	5
Not completed	1	0	0	0
Randomized but not treated	1	-	-	-

Period 2 title

Weeks 0-20

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer

Are arms mutually exclusive

Yes

Sitagliptin

Arm description

Arm type

Experimental

Investigational medicinal product name

Sitagliptin

Investigational medicinal product code

Other name

MK-0431

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Sitagliptin treatment arm received one tablet of sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Placebo matching Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria received metformin as glycemic Rescue Step 1 (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

In this period, participants in the Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.

Placebo/Metformin

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo matching Sitagliptin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Placebo matching Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Metformin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Metformin treatment arm meeting protocol-specific glycemic rescue criteria received metformin as glycemic Rescue Step 1 (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

In this period, participants in the Placebo/Metformin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.

Metformin

Arm description

In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20.

Arm type

Internal control

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Placebo matching Sitagliptin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Sitagliptin

Investigational medicinal product code

Other name

MK-0431

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Metformin treatment arm meeting protocol-specific glycemic rescue criteria received one tablet of sitagliptin 100 mg as glycemic Rescue Step 1.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

In this period, participants in the Metformin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.

Placebo/Sitagliptin

Arm description

In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20.

Arm type

Internal control

Investigational medicinal product name

Placebo matching Sitagliptin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Sitagliptin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Placebo matching Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Investigational medicinal product name

Sitagliptin

Investigational medicinal product code

Other name

MK-0431

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria received one tablet of sitagliptin 100 mg as glycemic Rescue Step 1.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

In this period, participants in the Placebo/Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Subjects reported in the baseline period (Weeks 0-20, Period 2) were in the all-subjects-as-treated population. The worldwide number of subjects enrolled in the trial was the same as the all-subjects-as-randomized population (Randomization, Period 1) . Baseline characteristics were available for the all-subjects-as-treated population (Weeks 0-20, Period 2).

Number of subjects in period 2 ^[2]	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Started	95	90	9	5
Completed	85	86	8	5
Not completed	10	4	1	0
Consent withdrawn by subject	3	2	1	-
Withdrawal by Parent/Guardian	5	2	-	-
Lost to follow-up	2	-	-	-

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Subjects reported in the baseline period (Weeks 0-20, Period 2) were in the all-subjects-as-treated population. The worldwide number of subjects enrolled in the trial was the same as the all-subjects-as-randomized population (Randomization, Period 1).

Period 3 title

Weeks 20-54

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer

Are arms mutually exclusive

Yes

Sitagliptin

Arm description

In this period, participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.

Arm type

Experimental

Investigational medicinal product name

Sitagliptin

Investigational medicinal product code

Other name

MK-0431

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Sitagliptin treatment arm received one tablet of sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Placebo matching Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Oral use

Dosage and administration details

Placebo/Metformin

Arm description

Arm type

Comparator

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Metformin treatment arm received two tablets of metformin prior to both the morning and evening meals (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).

Investigational medicinal product name

Placebo matching Sitagliptin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Sitagliptin

Investigational medicinal product code

Other name

MK-0431

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Metformin treatment arm meeting protocol-specific glycemic rescue criteria received one tablet of sitagliptin 100 mg as glycemic Rescue Step 1.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Metformin

Arm description

In this period, participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, but ongoing participants in this arm continued in the same arm during Weeks 20-54.

Arm type

Internal control

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Metformin treatment arm received two tablets of metformin prior to both the morning and evening meals.

Investigational medicinal product name

Placebo matching Sitagliptin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Sitagliptin

Investigational medicinal product code

Other name

MK-0431

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Metformin treatment arm meeting protocol-specific glycemic rescue criteria received one tablet of sitagliptin 100 mg as glycemic Rescue Step 1.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo/Sitagliptin

Arm description

In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, but ongoing participants in this arm continued in the same arm during Weeks 20-54.

Arm type

Comparator

Investigational medicinal product name

Sitagliptin

Investigational medicinal product code

Other name

MK-0431

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Sitagliptin treatment arm received one tablet of sitagliptin 100 mg prior to the morning meal.

Investigational medicinal product name

Placebo matching Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In this period, participants in the Placebo/Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria received metformin as glycemic Rescue Step 1 (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 3	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Started	85	86	8	5
Completed	74	78	6	5
Not completed	11	8	2	0
Consent withdrawn by subject	5	3	-	-
Withdrawal by Parent/Guardian	2	2	1	-
Lost to follow-up	4	3	1	-

Baseline characteristics

Top of page

Reporting group title

Sitagliptin

Reporting group description

Reporting group title

Placebo/Metformin

Reporting group description

Reporting group title

Metformin

Reporting group description

In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20.

Reporting group title

Placebo/Sitagliptin

Reporting group description

In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20.

Reporting group values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin	Total
Number of subjects	95	90	9	5	199
Age Categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	11	11	3	0	25
Adolescents (12-17 years)	84	79	6	5	174
Adults (18-64 years)	0	0	0	0	0
From 65-84 years	0	0	0	0	0
85 years and over	0	0	0	0	0
Unknown	0	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	14.3 ± 2.0	13.7 ± 1.9	13.3 ± 3.0	15.0 ± 1.6	-
Gender Categorical
Units: Subjects
Female	54	58	6	3	121
Male	41	32	3	2	78
Race
Units: Subjects
American Indian Or Alaska Native	6	9	0	0	15
Asian	13	14	1	2	30
Black Or African American	8	2	1	0	11
Multiple	20	18	1	0	39
White	48	47	6	3	104
Ethnicity
Units: Subjects
Hispanic Or Latino	36	33	2	2	73
Not Hispanic Or Latino	53	54	5	3	115
Unknown or Not Reported	6	3	2	0	11
Glycated Hemoglobin (A1C)
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. The analysis population includes all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C.
Units: Percentage
arithmetic mean (standard deviation)	7.43 ± 1.02	7.56 ± 1.08	7.43 ± 1.07	8.02 ± 0.75	-

Subject analysis set title

Sitagliptin

Subject analysis set type

Full analysis

Subject analysis set description

The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.

Subject analysis set title

Placebo/Metformin

Subject analysis set type

Full analysis

Subject analysis set description

The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.

Subject analysis set title

Metformin

Subject analysis set type

Full analysis

Subject analysis set description

The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.

Subject analysis set title

Placebo/Sitagliptin

Subject analysis set type

Full analysis

Subject analysis set description

The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.

Subject analysis set title

Placebo (pooled)

Subject analysis set type

Full analysis

Subject analysis set description

This analysis set, used only for analyses of data during Weeks 0-20, contains the pooled population of placebo-treated participants from the groups "Placebo/Sitagliptin" and "Placebo/Metformin".

Subject analysis sets values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin	Placebo (pooled)
Number of subjects	95	90	9	5	95
Age Categorical
Units: Subjects
In utero					0
Preterm newborn infants (gestational age < 37 wks)					0
Newborns (0-27 days)					0
Infants and toddlers (28 days-23 months)					0
Children (2-11 years)					11
Adolescents (12-17 years)					84
Adults (18-64 years)					0
From 65-84 years					0
85 years and over					0
Unknown					0
Age Continuous
Units: years
arithmetic mean (standard deviation)	±	±	±	±	13.7 ± 1.9
Gender Categorical
Units: Subjects
Female					61
Male					34
Race
Units: Subjects
American Indian Or Alaska Native					9
Asian					16
Black Or African American					2
Multiple					18
White					50
Ethnicity
Units: Subjects
Hispanic Or Latino					35
Not Hispanic Or Latino					57
Unknown or Not Reported					3
Glycated Hemoglobin (A1C)
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. The analysis population includes all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C.
Units: Percentage
arithmetic mean (standard deviation)	±	±	±	±	7.58 ± 1.06

End points

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Reporting group title

Sitagliptin

Reporting group description

In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.

Reporting group title

Placebo/Metformin

Reporting group description

Reporting group title

Metformin

Reporting group description

Reporting group title

Placebo/Sitagliptin

Reporting group description

Reporting group title

Sitagliptin

Reporting group description

Reporting group title

Placebo/Metformin

Reporting group description

Reporting group title

Metformin

Reporting group description

In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20.

Reporting group title

Placebo/Sitagliptin

Reporting group description

In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20.

Reporting group title

Sitagliptin

Reporting group description

Reporting group title

Placebo/Metformin

Reporting group description

Reporting group title

Metformin

Reporting group description

Reporting group title

Placebo/Sitagliptin

Reporting group description

Subject analysis set title

Sitagliptin

Subject analysis set type

Full analysis

Subject analysis set description

The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.

Subject analysis set title

Placebo/Metformin

Subject analysis set type

Full analysis

Subject analysis set description

The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.

Subject analysis set title

Metformin

Subject analysis set type

Full analysis

Subject analysis set description

The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.

Subject analysis set title

Placebo/Sitagliptin

Subject analysis set type

Full analysis

Subject analysis set description

The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.

Subject analysis set title

Placebo (pooled)

Subject analysis set type

Full analysis

Subject analysis set description

This analysis set, used only for analyses of data during Weeks 0-20, contains the pooled population of placebo-treated participants from the groups "Placebo/Sitagliptin" and "Placebo/Metformin".

Primary: Change from Baseline in Hemoglobin A1C (A1C) at Week 20

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End point title

Change from Baseline in Hemoglobin A1C (A1C) at Week 20 ^[1]

End point description

Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Primary

End point timeframe

Baseline and Week 20

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Summary data only was obtained for this primary end point, no between group statistical analysis was planned or performed.

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	78	70	8	3
Units: Percentage
arithmetic mean (standard deviation)	-0.13 ± 1.58	-0.02 ± 1.45	-1.03 ± 0.72	0.57 ± 1.62

No statistical analyses for this end point

Primary: Change from Baseline In A1C at Week 20 (Including Treatment Difference)

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End point title

Change from Baseline In A1C at Week 20 (Including Treatment Difference) ^[2]

End point description

Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C from a longitudinal data analysis model (LDA model). The analysis population included all randomized participants who received ≥1 dose of study medication and who had at least 1 measurement for the analysis endpoint.

End point type

Primary

End point timeframe

Baseline and Week 20

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Summary data only was obtained for this primary end point, no between group statistical analysis was planned or performed.

End point values	Sitagliptin	Placebo (pooled)
Number of subjects analysed	95	95
Units: Percentage
least squares mean (confidence interval 95%)	-0.01 (-0.35 to 0.34)	0.18 (-0.17 to 0.53)

Difference in Change from Baseline

Statistical analysis description

The Least Squares (LS) Mean for the arm "Sitagliptin" is compared against that of "Placebo (pooled)".

Comparison groups

Sitagliptin v Placebo (pooled)

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.448

Method

Mixed models analysis

Parameter type

Least Squares Means Difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.68

upper limit

0.3

Primary: Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56

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End point title

Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 ^[3]

End point description

The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The analysis population includes all randomized participants who received ≥1 dose of study medication.

End point type

Primary

End point timeframe

Up to Week 56

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Summary data only was obtained for this primary end point, no between group statistical analysis was planned or performed.

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	95	90	9	5
Units: Participants	73	67	7	4

No statistical analyses for this end point

Primary: Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Including Treatment Difference)

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End point title

Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Including Treatment Difference)

End point description

The percentage of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The analysis population includes all randomized participants who received ≥1 dose of study medication.

End point type

Primary

End point timeframe

Up to Week 56

End point values	Sitagliptin	Placebo/Metformin
Number of subjects analysed	95	90
Units: Percentage of participants
number (not applicable)	76.8	74.4

Difference in Percentage

Statistical analysis description

The percentage of participants who experienced ≥1 adverse event for the arm "Sitagliptin" is compared against that of "Placebo/Metformin". Analysis based on the Miettinen & Nurminen method.

Comparison groups

Sitagliptin v Placebo/Metformin

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Percentage

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-10

upper limit

14.9

Primary: Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54

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End point title

Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 ^[4]

End point description

The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The analysis population includes all randomized participants who received ≥1 dose of study medication.

End point type

Primary

End point timeframe

Up to Week 54

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Summary data only was obtained for this primary end point, no between group statistical analysis was planned or performed.

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	95	90	9	5
Units: Participants	5	1	0	0

No statistical analyses for this end point

Primary: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Including Treatment Difference)

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End point title

Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Including Treatment Difference)

End point description

The percentage of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The analysis population includes all randomized participants who received ≥1 dose of study medication.

End point type

Primary

End point timeframe

Up to Week 54

End point values	Sitagliptin	Placebo/Metformin
Number of subjects analysed	95	90
Units: Percentage of participants
number (not applicable)	5.3	1.1

Difference in percentage

Statistical analysis description

The percentage of participants who experienced ≥1 adverse event for the arm "Sitagliptin" is compared against that of "Placebo/Metformin". Analysis based on the Miettinen & Nurminen method.

Comparison groups

Sitagliptin v Placebo/Metformin

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in percentage

Point estimate

4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

10.8

Secondary: Change from Baseline in A1C at Week 54

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End point title

Change from Baseline in A1C at Week 54

End point description

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. This change from baseline reflects the Week 54 A1C minus the Week 0 A1C. The analysis population included all randomized participants who took at least one dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	41	48	4	1
Units: Percentage
arithmetic mean (standard deviation)	-0.19 ± 1.37	-0.90 ± 1.41	-0.70 ± 0.94	-0.50 ± 0.0

No statistical analyses for this end point

Secondary: Percentage of Participants With A1C at Goal (<7.0%) at Week 20

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End point title

Percentage of Participants With A1C at Goal (<7.0%) at Week 20

End point description

The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. All numbers shown in each individual treatment group are based on the observed values (Missing = Not at Goal). The analysis population included all randomized participants who received ≥1 dose of study medication.

End point type

Secondary

End point timeframe

Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	95	90	9	5
Units: Percentage of Participants
number (not applicable)	49.5	37.8	77.8	20.0

No statistical analyses for this end point

Secondary: Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Including Treatment Difference)

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End point title

Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Including Treatment Difference) ^[5]

End point description

The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. The analysis table includes the observed values for each treatment group (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The analysis population included all randomized participants who received ≥1 dose of study medication.

End point type

Secondary

End point timeframe

Week 20

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Summary data only was obtained for this primary end point, no between group statistical analysis was planned or performed.

End point values	Sitagliptin	Placebo (pooled)
Number of subjects analysed	95	95
Units: Percentage of participants
number (not applicable)	49.5	36.8

Difference in Percentage

Statistical analysis description

The percentage of participants with an A1C at the A1C goal (7.0%) in the arm "Sitagliptin" was compared against the arm "Placebo (pooled)". For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method based on the LDA model was used to impute whether the participant had met the goal.

Comparison groups

Sitagliptin v Placebo (pooled)

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.374

Method

Miettinen and Nurminen

Parameter type

Difference in percentage

Point estimate

6.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.1

upper limit

21.2

Secondary: Percentage of Participants With A1C at Goal (<6.5%) at Week 20

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End point title

Percentage of Participants With A1C at Goal (<6.5%) at Week 20

End point description

The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. All numbers shown in each individual treatment group are based on the observed values (Missing = Not at Goal). The analysis population included all randomized participants who received ≥1 dose of study medication.

End point type

Secondary

End point timeframe

Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	95	90	9	5
Units: Percentage of participants
number (not applicable)	30.5	23.3	66.7	20.0

No statistical analyses for this end point

Secondary: Percentage of Participants With A1C at Goal (<6.5) at Week 20 (Including Treatment Difference)

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End point title

Percentage of Participants With A1C at Goal (<6.5) at Week 20 (Including Treatment Difference) ^[6]

End point description

The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. The analysis table includes the observed values for each treatment group (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The analysis population included all randomized participants who received ≥1 dose of study medication.

End point type

Secondary

End point timeframe

Week 20

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Summary data only was obtained for this primary end point, no between group statistical analysis was planned or performed.

End point values	Sitagliptin	Placebo (pooled)
Number of subjects analysed	95	95
Units: Percentage of Participants
number (not applicable)	30.5	23.2

Difference in Percentage

Statistical analysis description

The percentage of participants with an A1C at the A1C goal (6.5%) in the arm "Sitagliptin" was compared against the arm "Placebo (pooled)". For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method based on the LDA model was used to impute whether the participant had met the goal. model.

Comparison groups

Sitagliptin v Placebo (pooled)

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.639

Method

Miettinen and Nurminen

Parameter type

Difference in percentage

Point estimate

3.6

Confidence interval

level

95%

sides

2-sided

lower limit

-11.6

upper limit

18.3

Secondary: Percentage of Participants With A1C at Goal (<7.0%) at Week 54

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End point title

Percentage of Participants With A1C at Goal (<7.0%) at Week 54

End point description

The percentage of participants with A1C at goal (<7.0%) at Week 54 was presented. All numbers shown in each individual treatment group are based on the observed values (Missing = Not at Goal). The analysis population included all randomized participants who received ≥1 dose of study medication.

End point type

Secondary

End point timeframe

Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	95	90	9	5
Units: Percentage of participants
number (not applicable)	28.4	40.0	33.3	20.0

No statistical analyses for this end point

Secondary: Percentage of Participants With A1C at Goal (<6.5%) at Week 54

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End point title

Percentage of Participants With A1C at Goal (<6.5%) at Week 54

End point description

The percentage of participants with A1C at goal (<6.5%) at Week 54 was presented. All numbers shown in each individual treatment group are based on the observed values (Missing = Not at Goal). The analysis population included all randomized participants who received ≥1 dose of study medication.

End point type

Secondary

End point timeframe

Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	95	90	9	5
Units: Percentage of participants
number (not applicable)	20.0	35.6	22.2	20.0

No statistical analyses for this end point

Secondary: Change from Baseline in Fasting Plasma Glucose (FPG) at Week 20

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End point title

Change from Baseline in Fasting Plasma Glucose (FPG) at Week 20

End point description

Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	81	74	8	3
Units: mg/dL
arithmetic mean (standard deviation)	9.98 ± 61.86	7.59 ± 41.11	-19.88 ± 49.78	57.67 ± 51.05

No statistical analyses for this end point

Secondary: Change from Baseline in FPG at Week 20 (Including Treatment Difference)

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End point title

Change from Baseline in FPG at Week 20 (Including Treatment Difference) ^[7]

End point description

Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline and was estimated from a longitudinal data analysis model. The analysis population includes all randomized participants who received ≥1 dose of study medication, and who had at least 1 measurement for the analysis endpoint.

End point type

Secondary

End point timeframe

Baseline and Week 20

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Summary data only was obtained for this primary end point, no between group statistical analysis was planned or performed.

End point values	Sitagliptin	Placebo (pooled)
Number of subjects analysed	95	95
Units: mg/dL
least squares mean (confidence interval 95%)	7.2 (-4.2 to 18.7)	5.7 (-6.0 to 17.4)

Difference in Change from Baseline

Statistical analysis description

The Least Squares (LS) Mean for the arm "Sitagliptin" was compared against that of "Placebo (pooled)".

Comparison groups

Sitagliptin v Placebo (pooled)

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.849

Method

Mixed models analysis

Parameter type

Least Squares Means Difference

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

17.5

Secondary: Change from Baseline in FPG at Week 54

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End point title

Change from Baseline in FPG at Week 54

End point description

Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 54 minus FPG at baseline. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	44	51	6	1
Units: mg/dL
arithmetic mean (standard deviation)	-3.03 ± 48.55	-4.52 ± 50.68	-29.92 ± 53.19	3.00 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20

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End point title

Change from Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20

End point description

PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour PMG minus the Week 0 2-hour PMG. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	12	12	4	2
Units: mg/dL
arithmetic mean (standard deviation)	-2.9 ± 42.6	2.1 ± 72.1	-6.8 ± 21.1	63.5 ± 171.8

No statistical analyses for this end point

Secondary: Change from Baseline in 2-hour PMG at Week 54

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End point title

Change from Baseline in 2-hour PMG at Week 54

End point description

PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour PMG minus the Week 0 2-hour PMG. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	8	3	1
Units: mg/dL
arithmetic mean (standard deviation)	-1.7 ± 21.3	-16.8 ± 48.9	-39.7 ± 32.3	-28.0 ± 0

No statistical analyses for this end point

Secondary: Change from Baseline in 2-hour Incremental PMG at Week 20

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End point title

Change from Baseline in 2-hour Incremental PMG at Week 20

End point description

2-Hour incremental PMG = Glucose at 120 minutes – glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour incremental PMG minus the Week 0 2-hour incremental PMG. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	12	12	4	2
Units: mg/dL
arithmetic mean (standard deviation)	1.5 ± 55.3	0.7 ± 35.9	0.8 ± 15.6	12.5 ± 98.3

No statistical analyses for this end point

Secondary: Change from Baseline in 2-Hour Incremental PMG at Week 54

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End point title

Change from Baseline in 2-Hour Incremental PMG at Week 54

End point description

2-Hour incremental PMG = Glucose at 120 minutes – glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour incremental PMG minus the Week 0 2-hour incremental PMG. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	8	3	1
Units: mg/dL
arithmetic mean (standard deviation)	-0.6 ± 64.6	-26.6 ± 39.0	-31.3 ± 34.8	-32.0 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin at Week 20 for Participants Not on Background Insulin

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End point title

Change from Baseline in Insulin at Week 20 for Participants Not on Background Insulin

End point description

This change from baseline reflects the Week 20 insulin minus the Week 0 insulin. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	67	58	7	3
Units: mIU/L
arithmetic mean (standard deviation)	1.59 ± 47.24	-3.91 ± 22.31	-7.25 ± 60.58	-1.23 ± 20.55

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin at Week 54 For Participants Not on Background Insulin

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End point title

Change from Baseline in Insulin at Week 54 For Participants Not on Background Insulin

End point description

This change from baseline reflects the Week 54 insulin minus the Week 0 insulin. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	37	45	5	1
Units: mIU/L
arithmetic mean (standard deviation)	-9.65 ± 40.82	-6.64 ± 32.01	-20.50 ± 65.08	-9.95 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin

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End point title

Change from Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin

End point description

This change from baseline reflects the Week 20 proinsulin minus the Week 0 proinsulin. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	68	57	7	3
Units: pmol/L
arithmetic mean (standard deviation)	0.91 ± 81.88	-10.88 ± 55.12	12.57 ± 36.98	-1.33 ± 9.07

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin

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End point title

Change from Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin

End point description

This change from baseline reflects the Week 54 proinsulin minus the Week 0 proinsulin. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	38	42	5	1
Units: pmol/L
arithmetic mean (standard deviation)	-10.62 ± 67.54	-16.13 ± 81.52	-23.30 ± 42.36	-0.50 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin

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End point title

Change from Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin

End point description

Change from baseline was the Week 20 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	65	55	6	3
Units: Ratio
arithmetic mean (standard deviation)	0.02 ± 0.22	0.02 ± 0.16	-0.03 ± 0.10	-0.19 ± 0.45

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin

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End point title

Change from Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin

End point description

The change from baseline was Week 54 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	36	41	5	1
Units: Ratio
arithmetic mean (standard deviation)	0.02 ± 0.23	-0.03 ± 0.19	-0.01 ± 0.06	0.02 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin

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End point title

Change from Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin

End point description

HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] – 3.5}. The change from baseline was Week 20 HOMA-β minus the Week 0 HOMA-β. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	67	58	7	3
Units: Percentage of Beta Cell Function
arithmetic mean (standard deviation)	15.72 ± 162.47	-53.23 ± 296.23	-1757.50 ± 4765.46	-64.78 ± 126.65

No statistical analyses for this end point

Secondary: Change from Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin

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End point title

Change from Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin

End point description

HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] – 3.5}. This change from baseline was Week 54 HOMA-β minus the Week 0 HOMA-β. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	36	45	5	1
Units: Percentage of Beta Cell Function
arithmetic mean (standard deviation)	-41.15 ± 183.17	-63.88 ± 339.74	-1860.69 ± 4099.22	-121.48 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin

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End point title

Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin

End point description

HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 20 HOMA-IR minus the Week 0 HOMA-IR. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	67	58	7	3
Units: mU*mmol/L^2
arithmetic mean (standard deviation)	-0.50 ± 31.62	-0.86 ± 9.02	-4.46 ± 34.65	2.58 ± 9.30

No statistical analyses for this end point

Secondary: Change from Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin

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End point title

Change from Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin

End point description

HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 54 HOMA-IR minus the Week 0 HOMA-IR. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	36	45	5	1
Units: mU * mmol/L^2
arithmetic mean (standard deviation)	-6.13 ± 34.86	-1.30 ± 15.31	-15.18 ± 36.41	-2.21 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20

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End point title

Change from Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	12	12	4	2
Units: mg*hr/dL
arithmetic mean (standard deviation)	-49.3 ± 103.6	2.0 ± 190.0	18.6 ± 50.9	191.0 ± 434.2

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin 3-hour AUC at Week 20

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End point title

Change from Baseline in Insulin 3-hour AUC at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	12	12	2	2
Units: µIU*hr/mL
arithmetic mean (standard deviation)	-14.5 ± 128.0	-32.8 ± 99.9	141.7 ± 206.1	-145.6 ± 180.6

No statistical analyses for this end point

Secondary: Change from Baseline in C-peptide 3-Hour AUC at Week 20

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End point title

Change from Baseline in C-peptide 3-Hour AUC at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	12	12	2	2
Units: ng*hr/mL
arithmetic mean (standard deviation)	-1.8 ± 4.9	-0.1 ± 3.3	5.9 ± 7.6	-6.4 ± 7.1

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin 3-Hour AUC at Week 20

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End point title

Change from Baseline in Proinsulin 3-Hour AUC at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 proinsulin 3-hour AUC minus the Week 0 proinsulin 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements. Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC. Proinsulin was collected only at a single time point and therefore AUC could not be derived.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	0 ^[8]	0 ^[9]	0 ^[10]	0 ^[11]
Units: pmol*hr/L
geometric mean (geometric coefficient of variation)	±	±	±	±

Notes
[8] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[9] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[10] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[11] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin 3-Hour AUC/Insulin 3-Hour AUC Ratio at Week 20

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End point title

Change from Baseline in Proinsulin 3-Hour AUC/Insulin 3-Hour AUC Ratio at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 proinsulin total AUC/insulin total AUC ratio minus the Week 0 proinsulin total AUC/insulin total AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements. Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC. Proinsulin was collected at only a single time point and therefore AUC could not be derived.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	0 ^[12]	0 ^[13]	0 ^[14]	0 ^[15]
Units: Ratio
geometric mean (geometric coefficient of variation)	±	±	±	±

Notes
[12] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[13] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[14] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[15] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20

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End point title

Change from Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin total AUC/glucose total AUC ratio minus the Week 0 insulin total AUC/glucose total AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	12	12	2	2
Units: [µIU*hr/mL]/[mg/dL]
arithmetic mean (standard deviation)	0.0 ± 0.3	-0.1 ± 0.3	0.2 ± 0.4	-0.2 ± 0.3

No statistical analyses for this end point

Secondary: Change from Baseline in Glucose Excursion 3-Hour AUC at Week 20

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End point title

Change from Baseline in Glucose Excursion 3-Hour AUC at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	12	12	4	2
Units: mg*hr/dL
arithmetic mean (standard deviation)	-43.5 ± 97.4	10.8 ± 58.6	39.8 ± 50.1	46.2 ± 201.9

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin Excursion 3-Hour AUC at Week 20

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End point title

Change from Baseline in Insulin Excursion 3-Hour AUC at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	12	12	2	2
Units: µIU*hr/mL
arithmetic mean (standard deviation)	-12.4 ± 89.4	-19.4 ± 93.6	87.5 ± 124.5	-82.8 ± 93.4

No statistical analyses for this end point

Secondary: Change from Baseline in C-peptide Excursion 3-Hour AUC at Week 20

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End point title

Change from Baseline in C-peptide Excursion 3-Hour AUC at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	12	12	2	2
Units: ng*hr/ml
arithmetic mean (standard deviation)	-1.1 ± 3.1	-0.4 ± 4.4	4.1 ± 5.6	-4.8 ± 5.2

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin Excursion 3-Hour AUC at Week 20

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End point title

Change from Baseline in Proinsulin Excursion 3-Hour AUC at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 proinsulin Excursion 3-hour AUC minus the Week 0 proinsulin Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements. Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	0 ^[16]	0 ^[17]	0 ^[18]	0 ^[19]
Units: pmol*hr/L
geometric mean (geometric coefficient of variation)	±	±	±	±

Notes
[16] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[17] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[18] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[19] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin Excursion 3-Hour AUC/Insulin Excursion 3-Hour AUC Ratio at Week 20

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End point title

Change from Baseline in Proinsulin Excursion 3-Hour AUC/Insulin Excursion 3-Hour AUC Ratio at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 proinsulin Excursion 3-hour AUC/insulin Excursion 3-hour AUC ratio minus the Week 0 proinsulin Excursion 3-hour AUC/insulin Excursion 3-hour AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements. Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	0 ^[20]	0 ^[21]	0 ^[22]	0 ^[23]
Units: Ratio
geometric mean (geometric coefficient of variation)	±	±	±	±

Notes
[20] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[21] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[22] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[23] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20

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End point title

Change from Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	11	10	2	2
Units: [µIU*hr/mL]/[mg/dL]
arithmetic mean (standard deviation)	2.2 ± 9.6	7.2 ± 17.5	-2.5 ± 3.2	1.4 ± 2.2

No statistical analyses for this end point

Secondary: Change from Baseline in Glucose 3-Hour AUC at Week 54

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End point title

Change from Baseline in Glucose 3-Hour AUC at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	8	3	1
Units: mg*hr/dL
arithmetic mean (standard deviation)	-21.1 ± 47.7	-36.0 ± 136.1	-73.1 ± 95.8	-63.3 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin 3-Hour AUC at Week 54

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End point title

Change from Baseline in Insulin 3-Hour AUC at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	8	2	1
Units: µIU*hr/mL
arithmetic mean (standard deviation)	-43.2 ± 259.8	-253.9 ± 282.7	-37.8 ± 9.4	-184.4 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in C-peptide 3-Hour AUC at Week 54

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End point title

Change from Baseline in C-peptide 3-Hour AUC at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	8	2	1
Units: ng*hr/ml
arithmetic mean (standard deviation)	-0.1 ± 5.7	-6.1 ± 8.2	1.7 ± 1.0	-8.9 ± 0

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin 3-Hour AUC at Week 54

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End point title

Change from Baseline in Proinsulin 3-Hour AUC at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 proinsulin 3-hour AUC minus the Week 0 proinsulin 3-hour AUC. The analysis population included all randomized who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements. Protocol Amendment 16 (12 June 2018) removed endpoints involving proinsulin analyzed as AUC.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	0 ^[24]	0 ^[25]	0 ^[26]	0 ^[27]
Units: pmol*hr/L
arithmetic mean (standard deviation)	±	±	±	±

Notes
[24] - Protocol Amendment 16 (12 June 2018) removed endpoints involving proinsulin analyzed as AUC.
[25] - Protocol Amendment 16 (12 June 2018) removed endpoints involving proinsulin analyzed as AUC.
[26] - Protocol Amendment 16 (12 June 2018) removed endpoints involving proinsulin analyzed as AUC.
[27] - Protocol Amendment 16 (12 June 2018) removed endpoints involving proinsulin analyzed as AUC.

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin 3-Hour AUC/Insulin 3-Hour AUC Ratio at Week 54

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End point title

Change from Baseline in Proinsulin 3-Hour AUC/Insulin 3-Hour AUC Ratio at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 proinsulin 3-hour AUC/insulin 3-hour AUC ratio minus the Week 0 proinsulin 3-hour AUC/insulin 3-hour AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements. Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	0 ^[28]	0 ^[29]	0 ^[30]	0 ^[31]
Units: Ratio
arithmetic mean (standard deviation)	±	±	±	±

Notes
[28] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[29] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[30] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[31] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54

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End point title

Change from Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC/glucose 3-hour AUC ratio minus the Week 0 insulin 3-hour AUC/glucose 3-hour AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	8	2	1
Units: [µIU*hr/mL]/[mg/dL]
arithmetic mean (standard deviation)	-0.1 ± 0.5	-0.6 ± 0.8	-0.0 ± 0.2	-0.3 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Glucose Excursion 3-Hour AUC at Week 54

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End point title

Change from Baseline in Glucose Excursion 3-Hour AUC at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	8	3	1
Units: mg*hr/dL
arithmetic mean (standard deviation)	-30.7 ± 100.7	-50.1 ± 79.5	-49.0 ± 87.5	-74.0 ± 0

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin Excursion 3-Hour AUC at Week 54

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End point title

Change from Baseline in Insulin Excursion 3-Hour AUC at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	8	2	1
Units: µIU*hr/mL
arithmetic mean (standard deviation)	-103.8 ± 151.0	-198.5 ± 263.0	-40.2 ± 11.5	-116.6 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in C-Peptide Excursion 3-Hour AUC at Week 54

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End point title

Change from Baseline in C-Peptide Excursion 3-Hour AUC at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	8	2	1
Units: ng*hr/ml
arithmetic mean (standard deviation)	-1.8 ± 3.0	-5.2 ± 8.8	0.9 ± 0.5	-5.9 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin Excursion 3-Hour AUC at Week 54

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End point title

Change from Baseline in Proinsulin Excursion 3-Hour AUC at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 proinsulin Excursion 3-hour AUC minus the Week 0 proinsulin Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for analysis endpoint at timepoint measurements. Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	0 ^[32]	0 ^[33]	0 ^[34]	0 ^[35]
Units: pmol*hr/L
arithmetic mean (standard deviation)	±	±	±	±

Notes
[32] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[33] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[34] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[35] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

No statistical analyses for this end point

Secondary: Change from Baseline in Proinsulin Excursion 3-Hour AUC/Insulin Excursion 3-Hour AUC Ratio at Week 54

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End point title

Change from Baseline in Proinsulin Excursion 3-Hour AUC/Insulin Excursion 3-Hour AUC Ratio at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 proinsulin Excursion 3-hour AUC/insulin Excursion 3-hour AUC ratio minus the Week 0 proinsulin Excursion 3-hour AUC/insulin Excursion 3-hour AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements. Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	0 ^[36]	0 ^[37]	0 ^[38]	0 ^[39]
Units: Ratio
arithmetic mean (standard deviation)	±	±	±	±

Notes
[36] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[37] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[38] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.
[39] - Protocol Amendment 16 removed endpoints involving proinsulin analyzed as AUC.

No statistical analyses for this end point

Secondary: Change from Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54

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End point title

Change from Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54

End point description

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	7	6	2	1
Units: [µIU*hr/mL]/[mg/dL]
arithmetic mean (standard deviation)	4.1 ± 13.1	3.7 ± 5.6	-2.7 ± 4.3	1.4 ± 0

No statistical analyses for this end point

Secondary: Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20

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End point title

Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20

End point description

The percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported. The analysis population included all randomized participants who received ≥1 dose of study medication.

End point type

Secondary

End point timeframe

Up to Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	95	90	9	5
Units: Percentage of participants
number (not applicable)	5.3	11.1	0.0	40.0

No statistical analyses for this end point

Secondary: Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54

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End point title

Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54

End point description

The percentage of participants who initiated glycemic rescue therapy prior to Week 54 was reported. The analysis population included all randomized participants who received ≥1 dose of study medication.

End point type

Secondary

End point timeframe

Up to Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	95	90	9	5
Units: Percentage of participants
number (not applicable)	35.8	28.9	11.1	80.0

No statistical analyses for this end point

Secondary: Change from Baseline in Body Mass Index (BMI) at Week 20

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End point title

Change from Baseline in Body Mass Index (BMI) at Week 20

End point description

This change from baseline was Week 20 BMI minus the Week 0 BMI. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	84	82	8	5
Units: kg/m^2
arithmetic mean (standard deviation)	0.0 ± 2.2	-0.7 ± 1.9	-0.8 ± 1.4	-1.7 ± 2.8

No statistical analyses for this end point

Secondary: Change from Baseline in BMI at Week 54

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End point title

Change from Baseline in BMI at Week 54

End point description

This change from baseline was Week 54 BMI minus the Week 0 BMI. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	72	73	6	5
Units: kg/m^2
arithmetic mean (standard deviation)	-0.4 ± 2.9	-1.0 ± 2.9	-0.6 ± 1.3	-0.3 ± 1.6

No statistical analyses for this end point

Secondary: Percent Change from Baseline in CD26 at Week 20

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End point title

Percent Change from Baseline in CD26 at Week 20

End point description

The percent change from baseline in CD26 = ([CD26 value at Week 20] - [baseline CD26 value] ÷ baseline CD26 value) × 100. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	68	57	4	3
Units: Percentage
arithmetic mean (standard deviation)	4.06 ± 19.25	-1.78 ± 17.18	4.89 ± 1.90	14.57 ± 15.46

No statistical analyses for this end point

Secondary: Percent Change from Baseline in CD26 at Week 54

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End point title

Percent Change from Baseline in CD26 at Week 54

End point description

The percent change from baseline in CD26 = ([CD26 value at Week 54] - [baseline CD26 value] ÷ baseline CD26 value) × 100. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	56	55	5	3
Units: Percentage
arithmetic mean (standard deviation)	4.74 ± 17.18	4.27 ± 18.24	12.63 ± 13.02	-5.30 ± 4.19

No statistical analyses for this end point

Secondary: Change from Baseline in Calcitonin at Week 20 - Females

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End point title

Change from Baseline in Calcitonin at Week 20 - Females

End point description

Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	43	46	4	2
Units: ng/L
arithmetic mean (standard deviation)	-0.1 ± 0.5	-2.0 ± 11.7	0.0 ± 0.0	0.0 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Calcitonin at Week 54 - Females

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End point title

Change from Baseline in Calcitonin at Week 54 - Females

End point description

Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	30	43	3	2
Units: ng/L
arithmetic mean (standard deviation)	-0.1 ± 0.6	-1.9 ± 12.1	0.0 ± 0.0	0.3 ± 0.4

No statistical analyses for this end point

Secondary: Change from Baseline in Calcitonin at Week 20 - Males

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End point title

Change from Baseline in Calcitonin at Week 20 - Males

End point description

Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	35	25	2	2
Units: ng/L
arithmetic mean (standard deviation)	0.2 ± 1.4	-0.2 ± 0.6	-1.6 ± 2.2	0.5 ± 0.6

No statistical analyses for this end point

Secondary: Change from Baseline in Calcitonin at Week 54 - Males

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End point title

Change from Baseline in Calcitonin at Week 54 - Males

End point description

Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	33	21	1	2
Units: ng/L
arithmetic mean (standard deviation)	0.1 ± 1.1	-0.3 ± 0.9	0.0 ± 0.0	1.4 ± 0.3

No statistical analyses for this end point

Secondary: Percent Change from Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females

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End point title

Percent Change from Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females

End point description

Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. The percent change from baseline in u-NTx/Creatinine ratio = ([u-NTx/Creatinine ratio at Week 20] - [baseline u-NTx/Creatinine ratio] ÷ baseline u-NTx/Creatinine ratio) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	33	31	4	3
Units: Percentage
arithmetic mean (standard deviation)	-28.7 ± 120.9	-41.2 ± 148.9	-98.0 ± 153.0	12.7 ± 29.2

No statistical analyses for this end point

Secondary: Percent Change from Baseline u-NTx/Creatinine Ratio at Week 20 - Males

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End point title

Percent Change from Baseline u-NTx/Creatinine Ratio at Week 20 - Males

End point description

Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. The percent change from baseline in u-NTx/Creatinine ratio = ([u-NTx/Creatinine ratio at Week 54] - [baseline u-NTx/Creatinine ratio] ÷ baseline u-NTx/Creatinine ratio) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	31	21	1	2
Units: Percentage
arithmetic mean (standard deviation)	-30.9 ± 167.2	-69.8 ± 162.1	62.0 ± 0.0	-29.0 ± 32.5

No statistical analyses for this end point

Secondary: Percent Change from Baseline in u-NTx/Creatinine Ratio at Week 54 - Females

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End point title

Percent Change from Baseline in u-NTx/Creatinine Ratio at Week 54 - Females

End point description

Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. The percent change from baseline in u-NTx/Creatinine ratio = ([u-NTx/Creatinine ratio at Week 54] - [baseline u-NTx/Creatinine ratio] ÷ baseline u-NTx/Creatinine ratio) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	28	30	4	3
Units: Percentage
arithmetic mean (standard deviation)	-88.4 ± 102.6	-61.2 ± 137.6	-80.3 ± 208.5	-17.0 ± 13.5

No statistical analyses for this end point

Secondary: Percent Change from Baseline in u-NTx/Creatinine Ratio at Week 54 - Males

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End point title

Percent Change from Baseline in u-NTx/Creatinine Ratio at Week 54 - Males

End point description

Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. The percent change from baseline in u-NTx/Creatinine ratio = ([u-NTx/Creatinine ratio at Week 20] - [baseline u-NTx/Creatinine ratio] ÷ baseline u-NTx/Creatinine ratio) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	30	16	0 ^[40]	1
Units: Percentage
arithmetic mean (standard deviation)	-78.2 ± 166.9	-102.4 ± 267.7	±	-30.0 ± 0.0

Notes
[40] - All participants in this arm were missing baseline or Week 54 measurements.

No statistical analyses for this end point

Secondary: Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females

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End point title

Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females

End point description

Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	43	52	5	3
Units: μg/L
arithmetic mean (standard deviation)	-6.0 ± 13.7	-4.2 ± 9.9	-9.7 ± 7.7	10.7 ± 9.7

No statistical analyses for this end point

Secondary: Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females

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End point title

Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females

End point description

Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	30	43	4	3
Units: μg/L
arithmetic mean (standard deviation)	-20.0 ± 28.4	-13.5 ± 18.1	-14.9 ± 10.3	-6.9 ± 9.2

No statistical analyses for this end point

Secondary: Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males

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End point title

Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males

End point description

Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	36	25	2	2
Units: μg/L
arithmetic mean (standard deviation)	-2.2 ± 21.6	0.1 ± 19.9	-7.1 ± 0.2	4.7 ± 8.2

No statistical analyses for this end point

Secondary: Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males

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End point title

Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males

End point description

Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	33	20	1	2
Units: μg/L
arithmetic mean (standard deviation)	-16.2 ± 28.0	-15.0 ± 27.0	-1.3 ± 0.0	-15.3 ± 12.4

No statistical analyses for this end point

Secondary: Percent Change from Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females

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End point title

Percent Change from Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females

End point description

IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value] ÷ baseline IGF-1 value) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	38	49	5	2
Units: Percentage
arithmetic mean (standard deviation)	0.5 ± 21.9	11.0 ± 34.0	-3.2 ± 14.9	41.4 ± 31.2

No statistical analyses for this end point

Secondary: Percent Change from Baseline in IGF-1 at Week 54 - Females

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End point title

Percent Change from Baseline in IGF-1 at Week 54 - Females

End point description

IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value] ÷ baseline IGF-1 value) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	30	42	4	1
Units: Percentage
arithmetic mean (standard deviation)	-1.5 ± 34.4	7.2 ± 57.6	-11.9 ± 13.4	-13.5 ± 0.0

No statistical analyses for this end point

Secondary: Percent Change from Baseline in IGF-1 at Week 20 - Males

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End point title

Percent Change from Baseline in IGF-1 at Week 20 - Males

End point description

IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value] ÷ baseline IGF-1 value) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	36	20	2	2
Units: Percentage
arithmetic mean (standard deviation)	-2.7 ± 22.1	9.3 ± 29.6	7.6 ± 17.4	5.3 ± 16.2

No statistical analyses for this end point

Secondary: Percent Change from Baseline in IGF-1 at Week 54 - Males

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End point title

Percent Change from Baseline in IGF-1 at Week 54 - Males

End point description

IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value] ÷ baseline IGF-1 value) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	32	18	1	2
Units: Percentage
arithmetic mean (standard deviation)	-4.9 ± 33.5	29.6 ± 99.8	18.8 ± 0.0	-6.8 ± 22.1

No statistical analyses for this end point

Secondary: Percent Change from Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females

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End point title

Percent Change from Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females

End point description

IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value] ÷ baseline IGF-BP3 value) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	41	50	6	2
Units: Percentage
arithmetic mean (standard deviation)	3.5 ± 18.2	3.8 ± 13.8	8.4 ± 12.9	-0.7 ± 24.1

No statistical analyses for this end point

Secondary: Percent Change from Baseline in IGF-BP3 at Week 54 - Females

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End point title

Percent Change from Baseline in IGF-BP3 at Week 54 - Females

End point description

IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value] ÷ baseline IGF-BP3 value) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	31	45	4	2
Units: Percentage
arithmetic mean (standard deviation)	2.0 ± 16.7	4.5 ± 17.0	11.4 ± 17.4	-13.4 ± 9.9

No statistical analyses for this end point

Secondary: Percent Change from Baseline in IGF-BP3 at Week 20 - Males

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End point title

Percent Change from Baseline in IGF-BP3 at Week 20 - Males

End point description

IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value] ÷ baseline IGF-BP3 value) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	36	24	2	2
Units: Percentage
arithmetic mean (standard deviation)	5.6 ± 13.3	10.2 ± 18.6	3.3 ± 0.5	14.2 ± 50.6

No statistical analyses for this end point

Secondary: Percent Change from Baseline in IGF-BP3 at Week 54 - Males

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End point title

Percent Change from Baseline in IGF-BP3 at Week 54 - Males

End point description

IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value] ÷ baseline IGF-BP3 value) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	32	21	1	2
Units: Percentage
arithmetic mean (standard deviation)	5.4 ± 18.4	18.2 ± 43.1	-2.9 ± 0.0	22.5 ± 8.3

No statistical analyses for this end point

Secondary: Growth Velocity at Week 20 - Females

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End point title

Growth Velocity at Week 20 - Females

End point description

Growth Velocity = change from baseline in height/change from baseline in chronologic age. The analysis population included all female randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	46	53	6	3
Units: cm/year
arithmetic mean (standard deviation)	3.2 ± 8.2	1.9 ± 2.7	5.0 ± 6.8	0.6 ± 1.6

No statistical analyses for this end point

Secondary: Growth Velocity at Week 54 - Females

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End point title

Growth Velocity at Week 54 - Females

End point description

End point type

Secondary

End point timeframe

Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	37	48	5	3
Units: cm/year
arithmetic mean (standard deviation)	2.1 ± 3.7	1.2 ± 1.8	2.4 ± 2.9	0.7 ± 1.0

No statistical analyses for this end point

Secondary: Growth Velocity at Week 20 - Males

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End point title

Growth Velocity at Week 20 - Males

End point description

Growth Velocity = change from baseline in height/change from baseline in chronologic age. The analysis population included all male randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	38	29	2	2
Units: cm/year
arithmetic mean (standard deviation)	2.6 ± 2.7	3.6 ± 3.2	-1.0 ± 1.3	1.7 ± 2.4

No statistical analyses for this end point

Secondary: Growth Velocity at Week 54 - Males

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End point title

Growth Velocity at Week 54 - Males

End point description

End point type

Secondary

End point timeframe

Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	35	25	1	2
Units: cm/year
arithmetic mean (standard deviation)	2.5 ± 2.5	2.8 ± 2.1	1.7 ± 0.0	2.8 ± 4.0

No statistical analyses for this end point

Secondary: Skeletal Maturation at Week 20 - Females

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End point title

Skeletal Maturation at Week 20 - Females

End point description

Skeletal Maturation = change from baseline in bone age/change from baseline in chronologic age. Bone age was determined from an X-ray of left hand and wrist. The analysis population included all female randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	17	18	3	2
Units: Ratio
arithmetic mean (standard deviation)	0.6 ± 1.9	0.4 ± 1.8	1.7 ± 2.3	-0.8 ± 5.5

No statistical analyses for this end point

Secondary: Skeletal Maturation at Week 54 - Females

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End point title

Skeletal Maturation at Week 54 - Females

End point description

Skeletal Maturation = change from baseline in bone age/change from baseline in chronologic age. Bone age was determined from X-ray of left hand and wrist. The analysis population included all female randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	8	14	3	0 ^[41]
Units: Ratio
arithmetic mean (standard deviation)	1.3 ± 1.1	1.0 ± 0.6	1.3 ± 2.2	±

Notes
[41] - All participants in this arm were missing baseline or Week 54 measurements.

No statistical analyses for this end point

Secondary: Skeletal Maturation at Week 20 - Males

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End point title

Skeletal Maturation at Week 20 - Males

End point description

Skeletal Maturation = change from baseline in bone age/change from baseline in chronologic age. Bone age was determined from X-ray of left hand and wrist. The analysis population included all male randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	13	17	1	1
Units: Ratio
arithmetic mean (standard deviation)	1.6 ± 1.7	1.2 ± 1.1	0.4 ± 0.0	2.4 ± 0.0

No statistical analyses for this end point

Secondary: Skeletal Maturation at Week 54 - Males

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End point title

Skeletal Maturation at Week 54 - Males

End point description

Skeletal Maturation = change from baseline in bone age/change from baseline in chronologic age. Bone age was determined from X-ray of left hand and wrist. The analysis population included all male randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	11	10	0 ^[42]	0 ^[43]
Units: Ratio
arithmetic mean (standard deviation)	1.3 ± 0.9	1.3 ± 0.6	±	±

Notes
[42] - All participants in this arm were missing baseline or Week 54 measurements.
[43] - All participants in this arm were missing baseline or Week 54 measurements.

No statistical analyses for this end point

Secondary: Change from Baseline in Tanner Staging for Genitalia at Week 20 - Males

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End point title

Change from Baseline in Tanner Staging for Genitalia at Week 20 - Males

End point description

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 20 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	31	29	1	2
Units: Score on a scale
arithmetic mean (standard deviation)	0.3 ± 0.5	0.2 ± 0.4	0.0 ± 0.0	0.5 ± 0.7

No statistical analyses for this end point

Secondary: Change from Baseline in Tanner Staging for Genitalia at Week 54 - Males

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End point title

Change from Baseline in Tanner Staging for Genitalia at Week 54 - Males

End point description

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 54 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	26	23	0 ^[44]	2
Units: Score on a scale
arithmetic mean (standard deviation)	0.5 ± 0.6	0.6 ± 0.7	±	0.5 ± 0.7

Notes
[44] - All participants in this arm were missing baseline or Week 54 measurements.

No statistical analyses for this end point

Secondary: Change from Baseline in Tanner Staging for Breasts at Week 20 - Females

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End point title

Change from Baseline in Tanner Staging for Breasts at Week 20 - Females

End point description

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 20 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	38	44	5	3
Units: Score on a Scale
arithmetic mean (standard deviation)	0.2 ± 0.6	0.1 ± 0.3	0.2 ± 0.4	0.3 ± 0.6

No statistical analyses for this end point

Secondary: Change from Baseline in Tanner Staging for Breasts at Week 54 - Females

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End point title

Change from Baseline in Tanner Staging for Breasts at Week 54 - Females

End point description

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 54 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	28	36	4	3
Units: Score on a Scale
arithmetic mean (standard deviation)	0.5 ± 0.7	0.4 ± 0.6	0.5 ± 1.0	0.7 ± 0.6

No statistical analyses for this end point

Secondary: Change from Baseline in Tanner Stage for Public Hair at Week 20 - Females

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End point title

Change from Baseline in Tanner Stage for Public Hair at Week 20 - Females

End point description

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development. Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	38	43	5	3
Units: Score on a scale
arithmetic mean (standard deviation)	0.1 ± 0.4	0.1 ± 0.3	0.2 ± 0.4	0.0 ± 0.0

No statistical analyses for this end point

Secondary: Change from Baseline in Tanner Stage for Pubic Hair at Week 54 - Females

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End point title

Change from Baseline in Tanner Stage for Pubic Hair at Week 54 - Females

End point description

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development with a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	28	35	4	3
Units: Score on a scale
arithmetic mean (standard deviation)	0.5 ± 0.6	0.3 ± 0.5	0.8 ± 1.5	0.3 ± 0.6

No statistical analyses for this end point

Secondary: Change from Baseline in Tanner Stage for Public Hair at Week 20 - Males

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End point title

Change from Baseline in Tanner Stage for Public Hair at Week 20 - Males

End point description

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development with a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	32	29	1	2
Units: Score on a scale
arithmetic mean (standard deviation)	0.3 ± 0.5	0.2 ± 0.4	0.0 ± 0.0	0.5 ± 0.7

No statistical analyses for this end point

Secondary: Change from Baseline in Tanner Stage for Pubic Hair at Week 54 - Males

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End point title

Change from Baseline in Tanner Stage for Pubic Hair at Week 54 - Males

End point description

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development with a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and timepoint measurements.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	26	23	0 ^[45]	2
Units: Score on a scale
arithmetic mean (standard deviation)	0.5 ± 0.7	0.6 ± 0.5	±	0.5 ± 0.7

Notes
[45] - All participants in this arm were missing baseline or Week 54 measurements.

No statistical analyses for this end point

Secondary: Percentage of Participants with Worsening in Dental Status at Week 20

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End point title

Percentage of Participants with Worsening in Dental Status at Week 20

End point description

Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening included participants with worsening of tooth fracture, tooth discoloration, or enamel defect as determined by the independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 20 dental assessments versus Baseline dental assessments. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at timepoint measurements.

End point type

Secondary

End point timeframe

Week 20

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	88	85	8	5
Units: Percentage of Participants
number (not applicable)
Participants with a dental assessment	69.3	71.8	25.0	40.0
1. With ≥1 tooth with worsening in any category	36.4	29.4	12.5	0
2. With ≥1 tooth with worsening fracture	5.7	5.9	0	0
3. With ≥1 tooth with worsening discoloration	33.0	27.1	0	0
4. With ≥1 tooth with worsening enamel defect	8.0	4.7	12.5	0

No statistical analyses for this end point

Secondary: Percentage of Participants with Worsening in Dental Status at Week 54

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End point title

Percentage of Participants with Worsening in Dental Status at Week 54

End point description

End point type

Secondary

End point timeframe

Week 54

End point values	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Number of subjects analysed	79	78	8	5
Units: Percentage of Participants
number (not applicable)
Participants with a dental assessment	74.7	75.6	25.0	40.0
1. With ≥1 tooth with worsening in any category	62.0	64.1	25.0	0
2. With ≥1 tooth with worsening fracture	16.5	19.2	12.5	0
3. With ≥1 tooth with worsening discoloration	57.0	61.5	25.0	0
4. With ≥1 with worsening enamel defect	16.5	16.7	12.5	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs: Up to approximately Week 56. Deaths and SAEs: Up to approximately 93 months.

Adverse event reporting additional description

The analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin treatment arm died after the treatment phases of the study at approximately 93 months.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

Sitagliptin

Reporting group description

Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.

Reporting group title

Placebo/Metformin

Reporting group description

Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.

Reporting group title

Metformin

Reporting group description

‌Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, but ongoing participants in this arm continued in this arm during Weeks 0-54.

Reporting group title

Placebo/Sitagliptin

Reporting group description

Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin arm, but ongoing participants in this arm continued in this arm during Weeks 0-54.

Serious adverse events	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 95 (10.53%)	7 / 90 (7.78%)	1 / 9 (11.11%)	3 / 5 (60.00%)
number of deaths (all causes)	1	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Investigations
Blood glucose increased
subjects affected / exposed	1 / 95 (1.05%)	0 / 90 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
subjects affected / exposed	1 / 95 (1.05%)	0 / 90 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leukaemia
subjects affected / exposed	1 / 95 (1.05%)	0 / 90 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Concussion
subjects affected / exposed	0 / 95 (0.00%)	1 / 90 (1.11%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Social circumstances
Sexual abuse
subjects affected / exposed	1 / 95 (1.05%)	0 / 90 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastritis
subjects affected / exposed	1 / 95 (1.05%)	0 / 90 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst ruptured
subjects affected / exposed	1 / 95 (1.05%)	0 / 90 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Erythema nodosum
subjects affected / exposed	0 / 95 (0.00%)	1 / 90 (1.11%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Affect lability
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 95 (0.00%)	1 / 90 (1.11%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess soft tissue
subjects affected / exposed	1 / 95 (1.05%)	0 / 90 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 95 (0.00%)	1 / 90 (1.11%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	0 / 95 (0.00%)	1 / 90 (1.11%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 95 (0.00%)	1 / 90 (1.11%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 95 (1.05%)	0 / 90 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 95 (0.00%)	1 / 90 (1.11%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 90 (1.11%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	3 / 95 (3.16%)	0 / 90 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Sitagliptin	Placebo/Metformin	Metformin	Placebo/Sitagliptin
Total subjects affected by non serious adverse events
subjects affected / exposed	62 / 95 (65.26%)	53 / 90 (58.89%)	7 / 9 (77.78%)	4 / 5 (80.00%)
Vascular disorders
Hypertension
subjects affected / exposed	2 / 95 (2.11%)	2 / 90 (2.22%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	2	2	1	0
General disorders and administration site conditions
Influenza like illness
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	0	0	4	0
Pyrexia
subjects affected / exposed	1 / 95 (1.05%)	6 / 90 (6.67%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	7	0	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	2 / 95 (2.11%)	1 / 90 (1.11%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences all number	2	2	0	1
Gynaecomastia
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Hyperventilation
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	2 / 95 (2.11%)	2 / 90 (2.22%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	2	2	1	0
Respiratory disorder
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Rhinorrhoea
subjects affected / exposed	1 / 95 (1.05%)	1 / 90 (1.11%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences all number	1	1	0	1
Investigations
Alanine aminotransferase increased
subjects affected / exposed	4 / 95 (4.21%)	3 / 90 (3.33%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences all number	4	3	0	1
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 95 (1.05%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	1	0	1	0
Tooth fracture
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Cardiac disorders
Wandering pacemaker
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	3 / 95 (3.16%)	2 / 90 (2.22%)	0 / 9 (0.00%)	2 / 5 (40.00%)
occurrences all number	5	2	0	4
Headache
subjects affected / exposed	9 / 95 (9.47%)	13 / 90 (14.44%)	2 / 9 (22.22%)	1 / 5 (20.00%)
occurrences all number	9	16	5	1
Eye disorders
Blepharitis
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Eye pain
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	8 / 95 (8.42%)	7 / 90 (7.78%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	10	10	1	0
Diarrhoea
subjects affected / exposed	8 / 95 (8.42%)	11 / 90 (12.22%)	2 / 9 (22.22%)	0 / 5 (0.00%)
occurrences all number	9	14	2	0
Dyspepsia
subjects affected / exposed	3 / 95 (3.16%)	2 / 90 (2.22%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	6	2	1	0
Nausea
subjects affected / exposed	5 / 95 (5.26%)	4 / 90 (4.44%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	5	5	1	0
Vomiting
subjects affected / exposed	6 / 95 (6.32%)	7 / 90 (7.78%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences all number	9	8	0	0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Nephrolithiasis
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	3 / 95 (3.16%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	3	0	1	0
Neck pain
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Pain in extremity
subjects affected / exposed	1 / 95 (1.05%)	1 / 90 (1.11%)	1 / 9 (11.11%)	1 / 5 (20.00%)
occurrences all number	1	1	1	1
Infections and infestations
Anal abscess
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Gastroenteritis
subjects affected / exposed	3 / 95 (3.16%)	7 / 90 (7.78%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	4	10	1	0
Influenza
subjects affected / exposed	2 / 95 (2.11%)	6 / 90 (6.67%)	1 / 9 (11.11%)	0 / 5 (0.00%)
occurrences all number	2	7	1	0
Nasopharyngitis
subjects affected / exposed	15 / 95 (15.79%)	6 / 90 (6.67%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences all number	19	6	0	0
Pertussis
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Pharyngitis
subjects affected / exposed	6 / 95 (6.32%)	6 / 90 (6.67%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences all number	7	6	0	0
Upper respiratory tract infection
subjects affected / exposed	12 / 95 (12.63%)	12 / 90 (13.33%)	1 / 9 (11.11%)	1 / 5 (20.00%)
occurrences all number	15	13	1	1
Urinary tract infection
subjects affected / exposed	4 / 95 (4.21%)	9 / 90 (10.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)
occurrences all number	4	11	0	0
Viral infection
subjects affected / exposed	0 / 95 (0.00%)	0 / 90 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	4
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	16 / 95 (16.84%)	12 / 90 (13.33%)	3 / 9 (33.33%)	2 / 5 (40.00%)
occurrences all number	107	37	65	3

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

27 May 2013

AM1 - Global amendment. Procedural and administrative changes.

25 Feb 2014

AM5 - Global amendment: Lengthened the Phase A placebo-controlled portion from 16 weeks to 20 weeks. Modified visit schedule to reduce the total number of visits from 13 to 11. Removed the metformin group and the placebo/sitagliptin group from the study. Based on revised power calculations, the sample size for the entire study was reduced from 360 participants to 170 participants – 2 treatment groups (sitagliptin or placebo) with 85 participants/group. Changed inclusion criterion of A1C from ≥7% to ≥6.5%. Modified the timeframe for prior treatment with insulin from 6 months to 12 weeks.

12 Feb 2015

AM7 - Global amendment. Included participants on background insulin.

01 Dec 2015

AM9 - Global amendment. Changed “adverse experience” to “adverse event.” Complied with recommendations from the US FDA to minimize missing data.

03 Feb 2017

AM12 - Global amendment. Added the dental substudy.

18 Jul 2018

AM16 - Global amendment. Complied with the recommendations from a health authority. Increased sample size. Clarified statistical methods for analyses using the Treatment Effect estimand. Added analyses using the Treatment Policy estimand.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in Hemoglobin A1C (A1C) at Week 20

Primary: Change from Baseline in Hemoglobin A1C (A1C) at Week 20

Primary: Change from Baseline In A1C at Week 20 (Including Treatment Difference)

Primary: Change from Baseline In A1C at Week 20 (Including Treatment Difference)

Primary: Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56

Primary: Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56

Primary: Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Including Treatment Difference)

Primary: Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Including Treatment Difference)

Primary: Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54

Primary: Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54

Primary: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Including Treatment Difference)

Primary: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Including Treatment Difference)

Secondary: Change from Baseline in A1C at Week 54

Secondary: Change from Baseline in A1C at Week 54

Secondary: Percentage of Participants With A1C at Goal (<7.0%) at Week 20

Secondary: Percentage of Participants With A1C at Goal (<7.0%) at Week 20

Secondary: Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Including Treatment Difference)

Secondary: Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Including Treatment Difference)

Secondary: Percentage of Participants With A1C at Goal (<6.5%) at Week 20

Secondary: Percentage of Participants With A1C at Goal (<6.5%) at Week 20

Secondary: Percentage of Participants With A1C at Goal (<6.5) at Week 20 (Including Treatment Difference)

Secondary: Percentage of Participants With A1C at Goal (<6.5) at Week 20 (Including Treatment Difference)

Secondary: Percentage of Participants With A1C at Goal (<7.0%) at Week 54

Secondary: Percentage of Participants With A1C at Goal (<7.0%) at Week 54

Secondary: Percentage of Participants With A1C at Goal (<6.5%) at Week 54

Secondary: Percentage of Participants With A1C at Goal (<6.5%) at Week 54

Secondary: Change from Baseline in Fasting Plasma Glucose (FPG) at Week 20

Secondary: Change from Baseline in Fasting Plasma Glucose (FPG) at Week 20

Secondary: Change from Baseline in FPG at Week 20 (Including Treatment Difference)

Secondary: Change from Baseline in FPG at Week 20 (Including Treatment Difference)

Secondary: Change from Baseline in FPG at Week 54

Secondary: Change from Baseline in FPG at Week 54

Secondary: Change from Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20

Secondary: Change from Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20

Secondary: Change from Baseline in 2-hour PMG at Week 54

Secondary: Change from Baseline in 2-hour PMG at Week 54

Secondary: Change from Baseline in 2-hour Incremental PMG at Week 20

Secondary: Change from Baseline in 2-hour Incremental PMG at Week 20

Secondary: Change from Baseline in 2-Hour Incremental PMG at Week 54

Secondary: Change from Baseline in 2-Hour Incremental PMG at Week 54

Secondary: Change from Baseline in Insulin at Week 20 for Participants Not on Background Insulin

Secondary: Change from Baseline in Insulin at Week 20 for Participants Not on Background Insulin

Secondary: Change from Baseline in Insulin at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in Insulin at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin

Secondary: Change from Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin

Secondary: Change from Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin

Secondary: Change from Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin

Secondary: Change from Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin

Secondary: Change from Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin

Secondary: Change from Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin

Secondary: Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin

Secondary: Change from Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin

Secondary: Change from Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20

Secondary: Change from Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20

Secondary: Change from Baseline in Insulin 3-hour AUC at Week 20

Secondary: Change from Baseline in Insulin 3-hour AUC at Week 20

Secondary: Change from Baseline in C-peptide 3-Hour AUC at Week 20

Secondary: Change from Baseline in C-peptide 3-Hour AUC at Week 20

Secondary: Change from Baseline in Proinsulin 3-Hour AUC at Week 20

Secondary: Change from Baseline in Proinsulin 3-Hour AUC at Week 20

Secondary: Change from Baseline in Proinsulin 3-Hour AUC/Insulin 3-Hour AUC Ratio at Week 20

Secondary: Change from Baseline in Proinsulin 3-Hour AUC/Insulin 3-Hour AUC Ratio at Week 20

Clinical Trial Results:
A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control