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Clinical Trial Results:
A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Patients with Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination with Insulin).

Summary
EudraCT number	2012-004035-23
Trial protocol	CZ IT HU DK BG Outside EU/EEA GR
Global end of trial date	17 Sep 2019

Results information
Results version number	v3(current)
This version publication date	15 Oct 2021
First version publication date	25 Mar 2020
Other versions	v1 , v2
Version creation reason	Correction of full data set Updates needed to study dates.

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

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Trial information

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Sponsor protocol code

0431A-289 and 0431A-170

ISRCTN number

US NCT number

NCT01760447

WHO universal trial number (UTN)

Other trial identifiers

EudraCT Number: 2011-002529-23, EudraCT Number: 2014-003583-20

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)

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

17 Sep 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

17 Sep 2019

Global end of trial reached?

Yes

Global end of trial date

17 Sep 2019

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to assess the effect of the addition of sitagliptin (administered as MK-0431A or MK-0431A XR) relative to the addition of placebo on glycated hemoglobin (A1C), and the safety and tolerability of the addition of sitagliptin, in pediatric participants (ages 10-17 years) with type 2 diabetes mellitus with inadequate glycemic control on metformin therapy (alone or in combination with insulin).

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 individual study was in place for the protection of trial subjects: Insulin as glycemic rescue therapy. In protocol MK-0431A-170, the type of insulin used as glycemic rescue therapy was at the investigator's discretion during Weeks 0-20, but only insulin glargine was used as glycemic rescue therapy during Weeks 20-54. In protocol MK-0431A-289, only insulin glargine was used as glycemic rescue therapy throughout Weeks 0-54.

Background therapy

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

Evidence for comparator

Actual start date of recruitment

07 Dec 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 1

Country: Number of subjects enrolled

Brazil: 1

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Chile: 4

Country: Number of subjects enrolled

Colombia: 2

Country: Number of subjects enrolled

Costa Rica: 4

Country: Number of subjects enrolled

Dominican Republic: 10

Country: Number of subjects enrolled

Guatemala: 8

Country: Number of subjects enrolled

Argentina: 1

Country: Number of subjects enrolled

Israel: 15

Country: Number of subjects enrolled

Malaysia: 22

Country: Number of subjects enrolled

Mauritius: 6

Country: Number of subjects enrolled

Mexico: 30

Country: Number of subjects enrolled

Philippines: 4

Country: Number of subjects enrolled

Russian Federation: 20

Country: Number of subjects enrolled

Saudi Arabia: 6

Country: Number of subjects enrolled

South Africa: 1

Country: Number of subjects enrolled

Sri Lanka: 23

Country: Number of subjects enrolled

Taiwan: 1

Country: Number of subjects enrolled

Thailand: 4

Country: Number of subjects enrolled

Ukraine: 8

Country: Number of subjects enrolled

United Arab Emirates: 4

Country: Number of subjects enrolled

United States: 31

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Greece: 1

Country: Number of subjects enrolled

Hungary: 2

Country: Number of subjects enrolled

Italy: 4

Country: Number of subjects enrolled

United Kingdom: 6

Worldwide total number of subjects

223

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)

202

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 28 countries. One participant randomized to the arm “Sitagliptin/Metformin” withdrew prior to treatment, then was re-randomized into the study. Both randomizations are counted for Subject Disposition and completion/non-completion is tracked as appropriate for both randomizations.

Screening details

The Pre-Assignment Period included a one-week single-blind placebo run-in prior to randomization during which participants received metformin with sitagliptin/metformin placebo or metformin XR with sitagliptin/metformin XR placebo each day.

Period 1 title

Randomization

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Assessor

Blinding implementation details

Participants enrolled in protocol MK-0431A-170 were aware that they would receive either sitagliptin and metformin, or metformin. Participants in protocol MK-0431A-289 were aware that they would receive either sitagliptin and metformin XR, or metformin XR.

Are arms mutually exclusive

Yes

Sitagliptin/Metformin

Arm description

Participants received one tablet of sitagliptin/metformin and one tablet of metformin-placebo, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170.

Arm type

Experimental

Investigational medicinal product name

Sitagliptin plus metformin

Investigational medicinal product code

Other name

MK-0431A

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1700 mg or 2000 mg of metformin. Dosage of metformin was based on each participant's daily metformin dose prior to enrollment.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue.

Investigational medicinal product name

Placebo to metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin.

Metformin

Arm description

Participants received one tablet of metformin and one tablet of placebo to sitagliptin/metformin, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170.

Arm type

Placebo

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 1000 mg, 1700 mg or 2000 mg of metformin. Dosage was based on each participant's daily metformin dose prior to enrollment.

Investigational medicinal product name

Placebo to sitagliptin plus metformin

Investigational medicinal product code

Other name

Placebo to MK-0431A

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to sitagliptin plus metformin.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue.

Sitagliptin/Metformin XR

Arm description

Participants received two tablets of sitagliptin/metformin XR and two tablets of metformin XR placebo, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289.

Arm type

Experimental

Investigational medicinal product name

Sitagliptin plus metformin XR

Investigational medicinal product code

Other name

MK-0431A XR

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1500 mg or 2000 mg of metformin. Dosage of metformin XR was based on each participant's daily metformin dose prior to enrollment.

Investigational medicinal product name

Placebo to metformin XR

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Metformin XR

Arm description

Participants received two tablets of metformin XR and two tablets of placebo to sitagliptin/metformin XR, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289.

Arm type

Placebo

Investigational medicinal product name

Placebo to sitagliptin plus metformin XR

Investigational medicinal product code

Other name

Placebo to MK-0431A XR

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to sitagliptin plus metformin XR.

Investigational medicinal product name

Metformin XR

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 1000 mg, 1500 mg or 2000 mg of metformin XR. Dosage was based on each participant's daily metformin dose prior to enrollment.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 1	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR
Started	63	62	47	51
Completed	62	62	45	51
Not completed	1	0	2	0
Randomized but not treated	1	-	2	-

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, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Sitagliptin/Metformin

Arm description

Participants received one tablet of sitagliptin/metformin and one tablet of metformin-placebo, administered twice daily prior to the morning and evening meals, during Weeks 0-20. Participants in this arm were enrolled in protocol MK-0431A-170.

Arm type

Experimental

Investigational medicinal product name

Sitagliptin plus metformin

Investigational medicinal product code

Other name

MK-0431A

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

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue.

Investigational medicinal product name

Placebo to metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin.

Metformin

Arm description

Participants received one tablet of metformin and one tablet of placebo to sitagliptin/metformin, administered twice daily prior to the morning and evening meals, during Weeks 0-20. Participants in this arm were enrolled in protocol MK-0431A-170.

Arm type

Placebo

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

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue.

Investigational medicinal product name

Placebo to sitagliptin plus metformin

Investigational medicinal product code

Other name

Placebo to MK-0431A

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to sitagliptin plus metformin.

Sitagliptin/Metformin XR

Arm description

Participants received two tablets of sitagliptin/metformin XR and two tablets of metformin XR placebo, administered once daily with a meal, during Weeks 0-20. Participants in this arm were enrolled in protocol MK-0431A-289.

Arm type

Experimental

Investigational medicinal product name

Sitagliptin plus metformin XR

Investigational medicinal product code

Other name

MK-0431A XR

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

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Investigational medicinal product name

Placebo to metformin XR

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR.

Metformin XR

Arm description

Participants received two tablets of metformin XR and two tablets of placebo to sitagliptin/metformin XR, administered once daily with a meal, during Weeks 0-20. Participants in this arm were enrolled in protocol MK-0431A-289.

Arm type

Placebo

Investigational medicinal product name

Placebo to sitagliptin plus metformin XR

Investigational medicinal product code

Other name

Placebo to MK-0431A XR

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to sitagliptin plus metformin XR.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Investigational medicinal product name

Metformin XR

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Period 1 includes all participants randomized. Period 2 includes all participants who were both randomized and treated with study medication, which is the population used for baseline characteristics.

Number of subjects in period 2 ^[2]	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR
Started	62	62	45	51
Treated	62	62	45	51
Completed	59	62	42	47
Not completed	3	0	3	4
Consent withdrawn by subject	2	-	1	-
Lost to follow-up	1	-	1	1
Consent withdrawn by Parent/Guardian	-	-	1	3

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: The baseline period used all participants both randomized and treated with study medication rather than all participants randomized, which was used as the worldwide total.

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, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Sitagliptin/Metformin

Arm description

Participants received one tablet of sitagliptin/metformin and one tablet of metformin-placebo, administered twice daily prior to the morning and evening meals, during Weeks 20-54. Participants in this arm were enrolled in protocol MK-0431A-170.

Arm type

Experimental

Investigational medicinal product name

Sitagliptin plus metformin

Investigational medicinal product code

Other name

MK-0431A

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

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue. During Weeks 20-54, for participants who were not on background insulin or rescued with insulin during Weeks 0-20 in the "Sitagliptin/Metformin" and "Metformin" arms (protocol MK-0431A-170), and during Weeks 0-54 for participants not on background insulin in the "Sitagliptin/Metformin XR" and "Metformin XR" arms (protocol MK-0431A-289), the type of insulin for glycemic rescue was specified to be insulin glargine.

Investigational medicinal product name

Placebo to metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin.

Metformin

Arm description

Participants received one tablet of metformin and one tablet of placebo to sitagliptin/metformin, administered twice daily prior to the morning and evening meals, during Weeks 20-54. Participants in this arm were enrolled in protocol MK-0431A-170.

Arm type

Placebo

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 to sitagliptin plus metformin

Investigational medicinal product code

Other name

Placebo to MK-0431A

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to sitagliptin plus metformin.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sitagliptin/Metformin XR

Arm description

Participants received two tablets of sitagliptin/metformin XR and two tablets of metformin XR placebo, administered once daily with a meal, during Weeks 20-54. Participants in this arm were enrolled in protocol MK-0431A-289.

Arm type

Experimental

Investigational medicinal product name

Sitagliptin plus metformin XR

Investigational medicinal product code

Other name

MK-0431A XR

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Placebo to metformin XR

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR.

Investigational medicinal product name

Insulin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Metformin XR

Arm description

Participants received two tablets of metformin XR and two tablets of placebo to sitagliptin/metformin XR, administered once daily with a meal, during Weeks 20-54. Participants in this arm were enrolled in protocol MK-0431A-289.

Arm type

Placebo

Investigational medicinal product name

Placebo to sitagliptin plus metformin XR

Investigational medicinal product code

Other name

Placebo to MK-0431A XR

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to sitagliptin plus metformin XR.

Investigational medicinal product name

Metformin XR

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

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 3 ^[3]	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR
Started	28	30	42	47
Completed	25	28	39	43
Not completed	3	2	3	4
Consent withdrawn by subject	2	1	1	2
Lost to follow-up	-	-	1	2
Consent withdrawn by Parent/Guardian	1	1	1	-

Notes
[3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: MK-0431A-170 added Weeks 20-54 via amendment, but not all participants were eligible for this period.

Baseline characteristics

Top of page

Reporting group title

Sitagliptin/Metformin

Reporting group description

Reporting group title

Metformin

Reporting group description

Reporting group title

Sitagliptin/Metformin XR

Reporting group description

Reporting group title

Metformin XR

Reporting group description

Reporting group values	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Total
Number of subjects	62	62	45	51	220
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)	10	7	3	1	21
Adolescents (12-17 years)	52	55	42	50	199
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
Age Continuous
Units: years
arithmetic mean (standard deviation)	14.4 ( 2.2 )	13.9 ( 1.8 )	14.8 ( 1.9 )	14.9 ( 1.6 )	-
Gender Categorical
Units: Subjects
Female	41	40	32	32	145
Male	21	22	13	19	75
Race
Units: Subjects
American Indian Or Alaska Native	0	1	3	9	13
Asian	21	22	15	6	64
Native Hawaiian or Other Pacific Islander	1	1	0	0	2
Black or African American	2	2	2	4	10
White	24	23	22	27	96
More than one race	14	13	3	5	35
Ethnicity
Units: Subjects
Hispanic or Latino	23	23	11	20	77
Not Hispanic or Latino	35	36	29	28	128
Unknown or Not Reported	4	3	5	3	15
Glycated Hemoglobin (A1C)
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. The analysis population includes all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C.
Units: Percentage of glycated hemoglobin
arithmetic mean (standard deviation)	8.02 ( 1.22 )	8.13 ( 1.08 )	7.87 ( 0.94 )	7.97 ( 1.05 )	-

Subject analysis set title

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled

Subject analysis set type

Full analysis

Subject analysis set description

This analysis set contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).

Subject analysis set title

Metformin and Metformin XR Pooled

Subject analysis set type

Full analysis

Subject analysis set description

This analysis set contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).

Subject analysis sets values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects	107	113
Age Categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	13	8
Adolescents (12-17 years)	94	105
Adults (18-64 years)	0	0
From 65-84 years	0	0
85 years and over	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	14.5 ( 2.1 )	14.4 ( 1.8 )
Gender Categorical
Units: Subjects
Female	73	72
Male	34	41
Race
Units: Subjects
American Indian Or Alaska Native	3	10
Asian	36	28
Native Hawaiian or Other Pacific Islander	1	1
Black or African American	4	6
White	46	50
More than one race	17	18
Ethnicity
Units: Subjects
Hispanic or Latino	34	43
Not Hispanic or Latino	64	64
Unknown or Not Reported	9	6
Glycated Hemoglobin (A1C)
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. The analysis population includes all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C.
Units: Percentage of glycated hemoglobin
arithmetic mean (standard deviation)	7.96 ( 1.11 )	8.06 ( 1.07 )

End points

Top of page

Reporting group title

Sitagliptin/Metformin

Reporting group description

Reporting group title

Metformin

Reporting group description

Reporting group title

Sitagliptin/Metformin XR

Reporting group description

Reporting group title

Metformin XR

Reporting group description

Reporting group title

Sitagliptin/Metformin

Reporting group description

Reporting group title

Metformin

Reporting group description

Reporting group title

Sitagliptin/Metformin XR

Reporting group description

Reporting group title

Metformin XR

Reporting group description

Reporting group title

Sitagliptin/Metformin

Reporting group description

Participants received one tablet of sitagliptin/metformin and one tablet of metformin-placebo, administered twice daily prior to the morning and evening meals, during Weeks 20-54. Participants in this arm were enrolled in protocol MK-0431A-170.

Reporting group title

Metformin

Reporting group description

Participants received one tablet of metformin and one tablet of placebo to sitagliptin/metformin, administered twice daily prior to the morning and evening meals, during Weeks 20-54. Participants in this arm were enrolled in protocol MK-0431A-170.

Reporting group title

Sitagliptin/Metformin XR

Reporting group description

Reporting group title

Metformin XR

Reporting group description

Subject analysis set title

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Metformin and Metformin XR Pooled

Subject analysis set type

Full analysis

Subject analysis set description

This analysis set contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).

Primary: Change from Baseline in A1C at Week 20

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End point title

Change from Baseline in A1C at Week 20

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. Mean change from baseline at Week 20 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 of A1C. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.

End point type

Primary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	107	113
Units: Percentage of glycated hemoglobin
least squares mean (confidence interval 95%)
Change from Baseline at Week 20	-0.58 (-0.94 to -0.22)	-0.09 (-0.43 to 0.26)

Difference in Change from Baseline

Statistical analysis description

The Least Squares (LS) Mean for the arm "Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled" is compared against that of "Metformin and Metformin XR Pooled."

Comparison groups

Metformin and Metformin XR Pooled v Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

-0.09

Primary: Number of participants who experienced ≥1 Adverse Event During Weeks 0-20

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End point title

Number of participants who experienced ≥1 Adverse Event During Weeks 0-20

End point description

The number of participants experiencing ≥1 adverse event during Weeks 0-20 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 20

End point values	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	62	62	45	51	107	113
Units: Participants	42	46	29	30	71	76

Difference in Percentage

Statistical analysis description

The percentage of participants who experienced ≥1 adverse event for the arm "Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled" is compared against that of "Metformin and Metformin XR Pooled."

Comparison groups

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled v Metformin and Metformin XR Pooled

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

Method

Miettinen and Nurminen

Parameter type

Difference in Percentage

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-13.9

upper limit

11.3

Primary: Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20

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End point title

Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20

End point description

The number of participants who discontinued from study drug due to an adverse event during Weeks 0-20 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 20

End point values	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	62	62	45	51	107	113
Units: Participants	1	2	2	2	3	4

Difference in Percentage

Statistical analysis description

The percentage of participants who discontinued study drug due to experiencing an adverse event for the arm "Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled" is compared against that of "Metformin and Metformin XR Pooled."

Comparison groups

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled v Metformin and Metformin XR Pooled

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

Method

Miettinen and Nurminen

Parameter type

Difference in Percentage

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

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

End point description

The number of participants experiencing ≥1 adverse event during Weeks 0-56 were 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 and continued in the study beyond Week 20.

End point type

Primary

End point timeframe

Up to approximately Week 56

End point values	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	28	30	42	47	70	77
Units: Participants	26	27	36	39	62	66

Difference in Percentage

Statistical analysis description

Comparison groups

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled v Metformin and Metformin XR Pooled

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

other

Method

Miettinen and Nurminen

Parameter type

Difference in Percentage

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-8.9

upper limit

14.4

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

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End point title

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

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 and continued in the study beyond Week 20.

End point type

Primary

End point timeframe

Up to Week 54

End point values	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	28	30	42	47	70	77
Units: Participants	1	1	1	3	2	4

Difference in Percentage

Statistical analysis description

Comparison groups

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled v Metformin and Metformin XR Pooled

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

other

Method

Miettinen and Nurminen

Parameter type

Difference in Percentage

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

5.8

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. Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model. The analysis population includes all randomized participants who received ≥1 dose of study medication, had ≥1 measurement of A1C, and continued in the study beyond Week 20. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and -289, pooled by receipt of experimental drug or placebo.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	70	77
Units: Percentage of glycated hemoglobin
least squares mean (confidence interval 95%)	0.35 (-0.48 to 1.19)	0.73 (-0.08 to 1.54)

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. Mean change from baseline at Week 20 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 of FPG. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	107	113
Units: mg/dL
least squares mean (confidence interval 95%)	-2.5 (-16.7 to 11.7)	8.3 (-5.0 to 21.6)

Difference in Change from Baseline

Statistical analysis description

The Least Squares (LS) Mean for the arm "Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled" is compared against that of "Metformin and Metformin XR Pooled."

Comparison groups

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled v Metformin and Metformin XR Pooled

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.159

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

-10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-25.9

upper limit

4.3

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. Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model. The analysis population includes all randomized participants who received ≥1 dose of study medication, had ≥1 measurement of FPG, and continued in the study beyond Week 20. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and -289, pooled by receipt of experimental drug or placebo.

End point type

Secondary

End point timeframe

Baseline and Week 54

End point values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	70	77
Units: mg/dL
least squares mean (confidence interval 95%)	16.8 (-8.4 to 42.0)	16.9 (-7.0 to 40.8)

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

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. Percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. The analysis population includes all randomized participants who received ≥1 dose of study medication. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.

End point type

Secondary

End point timeframe

Week 20

End point values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	107	113
Units: Percentage of participants
number (not applicable)	43.0	31.0

Difference in Percentage

Statistical analysis description

The percentage of participants with A1C at the A1C goal (<7.0%) in the arm "Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled" is compared against that of "Metformin and Metformin XR Pooled." For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method was used to impute whether the participant had met the goal.

Comparison groups

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled v Metformin and Metformin XR Pooled

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017

Method

Miettinen and Nurminen

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

2.9

upper limit

28.9

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

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. Percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. The analysis population includes all randomized participants who received ≥1 dose of study medication. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.

End point type

Secondary

End point timeframe

Week 20

End point values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	107	113
Units: Percentage of participants
number (not applicable)	29.0	20.4

Difference in Percentage

Statistical analysis description

The percentage of participants with A1C at the A1C goal (<6.5%) in the arm "Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled" is compared against that of "Metformin and Metformin XR Pooled." For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method was used to impute whether the participant had met the goal.

Comparison groups

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled v Metformin and Metformin XR Pooled

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.049

Method

Miettinen and Nurminen

Parameter type

Difference in Percentage

Point estimate

12.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

24.8

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

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. Percentage of participants with A1C at goal (<7.0%) at Week 54 was presented. The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.

End point type

Secondary

End point timeframe

Week 54

End point values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	70	77
Units: Percentage of participants
number (not applicable)	31.4	27.3

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

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. Percentage of participants with A1C at goal (<6.5%) at Week 54 was presented. The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.

End point type

Secondary

End point timeframe

Week 54

End point values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	70	77
Units: Percentage of participants
number (not applicable)	18.6	19.5

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

Percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported. The analysis population includes 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/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	62	62	45	51	107	113
Units: Percentage of participants
number (not applicable)	3.2	19.4	4.4	13.7	3.7	16.8

Difference in Percentage

Statistical analysis description

The percentage of participants initiating glycemic rescue therapy in the arm "Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled" is compared against that of "Metformin and Metformin XR Pooled."

Comparison groups

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled v Metformin and Metformin XR Pooled

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Log-Rank Test

Parameter type

Kaplan-Meier Difference in Percentage

Point estimate

-13.2

Confidence interval

level

95%

sides

2-sided

lower limit

-21.1

upper limit

-5.3

Secondary: Percentage of Participants Initiating Insulin Glargine During Weeks 20-54

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End point title

Percentage of Participants Initiating Insulin Glargine During Weeks 20-54

End point description

Percentage of participants who initiated insulin glargine therapy from Weeks 20 through 54 was reported. The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20 without initiating glycemic rescue therapy before Week 20. As defined in the protocols, these analyses were on participants pooled from protocols MK-0431A-170 and -289, pooled by receipt of drug or placebo.

End point type

Secondary

End point timeframe

Week 20 up to Week 54

End point values	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Number of subjects analysed	66	64
Units: Percentage of participants
number (not applicable)	22.7	26.6

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 56 weeks for non-serious adverse events. Up to approximately 76 weeks for serious adverse events. Up to approximately 78 weeks for deaths.

Adverse event reporting additional description

"Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled" = "Sitagliptin/Metformin" plus "Sitagliptin/Metformin XR." "Metformin and Metformin XR Pooled" = "Metformin" plus "Metformin XR." Non-serious and serious adverse events are recorded for all treated participants

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Sitagliptin/Metformin

Reporting group description

Reporting group title

Metformin

Reporting group description

Reporting group title

Sitagliptin/Metformin XR

Reporting group description

Reporting group title

Metformin XR

Reporting group description

Reporting group title

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled

Reporting group description

Reporting group title

Metformin and Metformin XR Pooled

Reporting group description

Serious adverse events	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 62 (6.45%)	3 / 62 (4.84%)	3 / 45 (6.67%)	3 / 51 (5.88%)	7 / 107 (6.54%)	6 / 113 (5.31%)
number of deaths (all causes)	1	0	0	0	1	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Investigations
Blood glucose increased
subjects affected / exposed	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 45 (0.00%)	0 / 51 (0.00%)	0 / 107 (0.00%)	1 / 113 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Epilepsy
subjects affected / exposed	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 45 (0.00%)	0 / 51 (0.00%)	0 / 107 (0.00%)	1 / 113 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 45 (0.00%)	0 / 51 (0.00%)	1 / 107 (0.93%)	0 / 113 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Immune system disorders
Type I hypersensitivity
subjects affected / exposed	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 45 (0.00%)	0 / 51 (0.00%)	1 / 107 (0.93%)	0 / 113 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 45 (0.00%)	1 / 51 (1.96%)	0 / 107 (0.00%)	1 / 113 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 45 (2.22%)	0 / 51 (0.00%)	1 / 107 (0.93%)	0 / 113 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 45 (0.00%)	1 / 51 (1.96%)	0 / 107 (0.00%)	1 / 113 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 45 (0.00%)	0 / 51 (0.00%)	1 / 107 (0.93%)	0 / 113 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicide attempt
subjects affected / exposed	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 45 (0.00%)	1 / 51 (1.96%)	0 / 107 (0.00%)	1 / 113 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Synovial cyst
subjects affected / exposed	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 45 (0.00%)	0 / 51 (0.00%)	1 / 107 (0.93%)	0 / 113 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 45 (2.22%)	0 / 51 (0.00%)	1 / 107 (0.93%)	0 / 113 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
H1N1 influenza
subjects affected / exposed	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 45 (0.00%)	1 / 51 (1.96%)	0 / 107 (0.00%)	1 / 113 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 45 (0.00%)	0 / 51 (0.00%)	1 / 107 (0.93%)	0 / 113 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 45 (2.22%)	0 / 51 (0.00%)	1 / 107 (0.93%)	0 / 113 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 45 (0.00%)	1 / 51 (1.96%)	0 / 107 (0.00%)	2 / 113 (1.77%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Total subjects affected by non serious adverse events
subjects affected / exposed	34 / 62 (54.84%)	40 / 62 (64.52%)	30 / 45 (66.67%)	36 / 51 (70.59%)	64 / 107 (59.81%)	76 / 113 (67.26%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 62 (3.23%)	3 / 62 (4.84%)	3 / 45 (6.67%)	3 / 51 (5.88%)	5 / 107 (4.67%)	6 / 113 (5.31%)
occurrences all number	3	3	3	3	6	6
Blood creatine phosphokinase increased
subjects affected / exposed	3 / 62 (4.84%)	1 / 62 (1.61%)	3 / 45 (6.67%)	1 / 51 (1.96%)	6 / 107 (5.61%)	2 / 113 (1.77%)
occurrences all number	3	1	3	1	6	2
Blood glucose increased
subjects affected / exposed	3 / 62 (4.84%)	0 / 62 (0.00%)	2 / 45 (4.44%)	3 / 51 (5.88%)	5 / 107 (4.67%)	3 / 113 (2.65%)
occurrences all number	4	0	2	5	6	5
Creatinine renal clearance increased
subjects affected / exposed	4 / 62 (6.45%)	0 / 62 (0.00%)	0 / 45 (0.00%)	0 / 51 (0.00%)	4 / 107 (3.74%)	0 / 113 (0.00%)
occurrences all number	4	0	0	0	4	0
Urine albumin/creatinine ratio increased
subjects affected / exposed	4 / 62 (6.45%)	2 / 62 (3.23%)	0 / 45 (0.00%)	0 / 51 (0.00%)	4 / 107 (3.74%)	2 / 113 (1.77%)
occurrences all number	5	2	0	0	5	2
Nervous system disorders
Headache
subjects affected / exposed	3 / 62 (4.84%)	8 / 62 (12.90%)	2 / 45 (4.44%)	10 / 51 (19.61%)	5 / 107 (4.67%)	18 / 113 (15.93%)
occurrences all number	4	10	4	15	8	25
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 62 (3.23%)	4 / 62 (6.45%)	4 / 45 (8.89%)	4 / 51 (7.84%)	6 / 107 (5.61%)	8 / 113 (7.08%)
occurrences all number	2	4	4	4	6	8
Abdominal pain upper
subjects affected / exposed	1 / 62 (1.61%)	2 / 62 (3.23%)	0 / 45 (0.00%)	3 / 51 (5.88%)	1 / 107 (0.93%)	5 / 113 (4.42%)
occurrences all number	2	2	0	4	2	6
Diarrhoea
subjects affected / exposed	7 / 62 (11.29%)	4 / 62 (6.45%)	1 / 45 (2.22%)	3 / 51 (5.88%)	8 / 107 (7.48%)	7 / 113 (6.19%)
occurrences all number	8	4	1	10	9	14
Nausea
subjects affected / exposed	2 / 62 (3.23%)	5 / 62 (8.06%)	4 / 45 (8.89%)	2 / 51 (3.92%)	6 / 107 (5.61%)	7 / 113 (6.19%)
occurrences all number	5	5	6	3	11	8
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 62 (3.23%)	3 / 62 (4.84%)	3 / 45 (6.67%)	2 / 51 (3.92%)	5 / 107 (4.67%)	5 / 113 (4.42%)
occurrences all number	2	4	3	2	5	6
Oropharyngeal pain
subjects affected / exposed	2 / 62 (3.23%)	1 / 62 (1.61%)	3 / 45 (6.67%)	1 / 51 (1.96%)	5 / 107 (4.67%)	2 / 113 (1.77%)
occurrences all number	2	1	3	6	5	7
Infections and infestations
Gastroenteritis
subjects affected / exposed	5 / 62 (8.06%)	3 / 62 (4.84%)	3 / 45 (6.67%)	2 / 51 (3.92%)	8 / 107 (7.48%)	5 / 113 (4.42%)
occurrences all number	6	3	3	2	9	5
Influenza
subjects affected / exposed	1 / 62 (1.61%)	4 / 62 (6.45%)	2 / 45 (4.44%)	3 / 51 (5.88%)	3 / 107 (2.80%)	7 / 113 (6.19%)
occurrences all number	1	5	3	5	4	10
Nasopharyngitis
subjects affected / exposed	7 / 62 (11.29%)	7 / 62 (11.29%)	1 / 45 (2.22%)	2 / 51 (3.92%)	8 / 107 (7.48%)	9 / 113 (7.96%)
occurrences all number	11	7	2	3	13	10
Pharyngitis
subjects affected / exposed	1 / 62 (1.61%)	3 / 62 (4.84%)	1 / 45 (2.22%)	5 / 51 (9.80%)	2 / 107 (1.87%)	8 / 113 (7.08%)
occurrences all number	1	3	1	6	2	9
Upper respiratory tract infection
subjects affected / exposed	9 / 62 (14.52%)	6 / 62 (9.68%)	5 / 45 (11.11%)	3 / 51 (5.88%)	14 / 107 (13.08%)	9 / 113 (7.96%)
occurrences all number	11	8	9	5	20	13
Urinary tract infection
subjects affected / exposed	0 / 62 (0.00%)	5 / 62 (8.06%)	3 / 45 (6.67%)	1 / 51 (1.96%)	3 / 107 (2.80%)	6 / 113 (5.31%)
occurrences all number	0	6	3	1	3	7
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	3 / 62 (4.84%)	5 / 62 (8.06%)	3 / 45 (6.67%)	4 / 51 (7.84%)	6 / 107 (5.61%)	9 / 113 (7.96%)
occurrences all number	3	6	3	4	6	10
Hypoglycaemia
subjects affected / exposed	10 / 62 (16.13%)	6 / 62 (9.68%)	9 / 45 (20.00%)	10 / 51 (19.61%)	19 / 107 (17.76%)	16 / 113 (14.16%)
occurrences all number	106	15	70	45	176	60

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

21 Sep 2012

MK-0431A-170 AM01 (Base study): Incorporated procedural and administrative changes.

17 Apr 2014

MK-0431A-170 AM02 (Base study): Updated analyses to reflect the pooled analysis. Reduced the sample size from 240 to 90 participants and analysis was combined with study MK-0431A-289 with adequate power for the primary analysis at Week 20. The timeframe required for participants to be off insulin therapy before Visit 1 was reduced from 6 months to 12 weeks. A1C lower limit for inclusion changed from ≥7.0% to ≥6.5%.

17 Apr 2014

MK-0431A-170 AM03 (Extension study): Created the 34-week extension study.

17 Apr 2014

MK-0431A-289 AM04: Modified the timeframe for prior treatment with insulin from 6 months to 12 weeks. A1C lower limit for inclusion changed from ≥7% to ≥6.5%. Sample size was reduced from 240 to 90 participants and analysis was combined with study MK-0431A-170 with adequate power for the primary analysis at Week 20.

09 Jan 2015

MK-0431A-170 AM04 (Base study): Included participants on background insulin.

09 Jan 2015

MK-0431A-170 AM05 (Extension study): Included participants on background insulin.

20 Jan 2015

MK-0431A-289 AM05: Included participants on background insulin.

10 Apr 2015

MK-0431A-170 AM07 (Base study): Changed “adverse experience” to “adverse event.”

10 Apr 2015

MK-0431A-170 AM08 (Extension study): Changed “adverse experience” to “adverse event.”

09 Sep 2015

MK-0431A-289 AM07: Changed “adverse experience” to “adverse event.” Complied with recommendations from the FDA to minimize missing data.

04 Nov 2015

MK-0431A-170 AM11 (Base study): Complied with recommendations from the FDA to minimize missing data. Updated sample size from approximately 90 participants to approximately 130 participants.

04 Nov 2015

MK-0431A-170 AM12 (Extension study): Complied with recommendations from the FDA to minimize missing data. Updated sample size from approximately 90 participants to approximately 130 participants.

12 Apr 2018

MK-0431A-170 AM15 (Base study): Modified sample size. Beginning and end of study were defined. Clarified statistical methods for analyses using the Treatment Effect estimand. Added analyses using the Treatment Policy estimand.

12 Apr 2018

MK-0431A-170 AM16 (Extension study): Modified sample size. Beginning and end of study were defined.

12 Apr 2018

MK-0431A-289 AM10: 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 Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Patients with Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination with Insulin).

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in A1C at Week 20

Primary: Change from Baseline in A1C at Week 20

Primary: Number of participants who experienced ≥1 Adverse Event During Weeks 0-20

Primary: Number of participants who experienced ≥1 Adverse Event During Weeks 0-20

Primary: Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20

Primary: Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20

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

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

Secondary: Change from baseline in A1C at Week 54

Secondary: Change from baseline in A1C 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 54

Secondary: Change from Baseline in FPG 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 (<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 (<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: Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20

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

Secondary: Percentage of Participants Initiating Insulin Glargine During Weeks 20-54

Secondary: Percentage of Participants Initiating Insulin Glargine During Weeks 20-54

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Patients with Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination with Insulin).