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    Clinical Trial Results:
    A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of Ertugliflozin (MK-8835/PF-04971729) with Sitagliptin Compared with Ertugliflozin Alone and Sitagliptin Alone, in the Treatment of Subjects with T2DM With Inadequate Glycemic Control on Metformin Monotherapy

    Summary
    EudraCT number
    		 2013-003698-82
    Trial protocol
    		 HU   CZ   IT   GB   FI   SK   BG   PL  
    Global end of trial date
    26 May 2016

    Results information
    Results version number
    		 v2(current)
    This version publication date
    07 Sep 2017
    First version publication date
    12 May 2017
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    8835-005
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02099110
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 MK-8835-005: Merck protocol number, B1521015: Pfizer protocol number, VERTIS FACTORIAL: Study Name
    Sponsors
    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
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 May 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 May 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This is a study of co-administration of ertugliflozin (MK-8835/PF-04971729) and sitagliptin given together or alone along with metformin in participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin monotherapy. The primary hypothesis of this study is that ertugliflozin 5 mg or 15 mg daily plus sitagliptin 100 mg daily provides greater hemoglobin A1C (A1C) -lowering compared with sitagliptin 100 mg daily alone.
    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. Participants who meet pre-specified glycemic criteria and who are rescued will receive oral tablets of open-label glimepiride or insulin glargine injected subcutaneously at dose strengths determined by the investigator.
    Background therapy
    		 For participants requiring metformin dose adjustment, metformin will be titrated over a period of up-to 4 weeks before the required dose-stabilization period (≥8 weeks) begins. While receiving blinded investigational product during the double-blind treatment period, participants will also receive metformin >= 1500 mg/day, tablets, oral, for 52 weeks.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Apr 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 89
    Country: Number of subjects enrolled
    Bulgaria: 41
    Country: Number of subjects enrolled
    Canada: 38
    Country: Number of subjects enrolled
    Chile: 40
    Country: Number of subjects enrolled
    Colombia: 10
    Country: Number of subjects enrolled
    Czech Republic: 35
    Country: Number of subjects enrolled
    Finland: 7
    Country: Number of subjects enrolled
    Hungary: 36
    Country: Number of subjects enrolled
    Israel: 35
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Malaysia: 27
    Country: Number of subjects enrolled
    Mexico: 71
    Country: Number of subjects enrolled
    New Zealand: 21
    Country: Number of subjects enrolled
    Philippines: 45
    Country: Number of subjects enrolled
    Poland: 87
    Country: Number of subjects enrolled
    Romania: 84
    Country: Number of subjects enrolled
    Russian Federation: 96
    Country: Number of subjects enrolled
    Slovakia: 58
    Country: Number of subjects enrolled
    Thailand: 9
    Country: Number of subjects enrolled
    Ukraine: 64
    Country: Number of subjects enrolled
    United States: 338
    Worldwide total number of subjects
    1233
    EEA total number of subjects
    350
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    1034
    From 65 to 84 years
    199
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial was conducted in 21 countries and included 242 trial centers.

    Pre-assignment
    Screening details
    		 Male and female participants with T2DM of at least 18 years of age were enrolled in this trial. Participants on ≥1500 mg/day of metformin for ≥8 weeks with A1C ≥7.5 and ≤11% at screening could directly enter a 2-week, single-blind, placebo run-in period. Participants who did not meet these criteria received metformin titration for ~8 weeks.

    Period 1
    Period 1 title
    Overall Study Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ertugliflozin 5 mg
    Arm description
    		 Ertugliflozin 5 mg once daily, placebo to ertugliflozin once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ertugliflozin
    Investigational medicinal product code
    Other name
    MK-8835, PF-04971729
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ertugliflozin, 5 mg, once daily, orally for 52 weeks

    Investigational medicinal product name
    Placebo to ertugliflozin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to ertugliflozin once daily for 52 weeks

    Investigational medicinal product name
    Placebo to sitagliptin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to sitagliptin once daily for 52 weeks

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Glucophage Glucophage XR
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    For participants requiring metformin dose adjustment, metformin will be titrated over a period of up-to 4 weeks before the required dose-stabilization period (≥8 weeks) begins. While receiving blinded investigational product during the double-blind treatment period, participants will also receive metformin >= 1500 mg/day, tablets, oral, for 52 weeks.

    Investigational medicinal product name
    Insulin Glargine Rescue Medication
    Investigational medicinal product code
    Other name
    Lantus
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion

    Investigational medicinal product name
    Glimepiride Rescue Medication
    Investigational medicinal product code
    Other name
    AMARYL
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion

    Arm title
    		 Ertugliflozin 15 mg
    Arm description
    		 Ertugliflozin 15 mg once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ertugliflozin
    Investigational medicinal product code
    Other name
    MK-8835, PF-04971729
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ertugliflozin 15 mg once daily, for 52 weeks

    Investigational medicinal product name
    Placebo to sitagliptin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to sitagliptin once daily for 52 weeks

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Glucophage Glucophage XR
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    For participants requiring metformin dose adjustment, metformin will be titrated over a period of up-to 4 weeks before the required dose-stabilization period (≥8 weeks) begins. While receiving blinded investigational product during the double-blind treatment period, participants will also receive metformin >= 1500 mg/day, tablets, oral, for 52 weeks.

    Investigational medicinal product name
    Insulin Glargine Rescue Medication
    Investigational medicinal product code
    Other name
    Lantus
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion

    Investigational medicinal product name
    Glimepiride Rescue Medication
    Investigational medicinal product code
    Other name
    AMARYL
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion

    Arm title
    		 Sitagliptin 100 mg
    Arm description
    		 Sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Sitagliptin
    Investigational medicinal product code
    Other name
    JANUVIA®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Sitagliptin 100 mg once daily, for 52 weeks

    Investigational medicinal product name
    Placebo to ertugliflozin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to ertugliflozin once daily for 52 weeks

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Glucophage Glucophage XR
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    For participants requiring metformin dose adjustment, metformin will be titrated over a period of up-to 4 weeks before the required dose-stabilization period (≥8 weeks) begins. While receiving blinded investigational product during the double-blind treatment period, participants will also receive metformin >= 1500 mg/day, tablets, oral, for 52 weeks.

    Investigational medicinal product name
    Insulin Glargine Rescue Medication
    Investigational medicinal product code
    Other name
    Lantus
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion

    Investigational medicinal product name
    Glimepiride Rescue Medication
    Investigational medicinal product code
    Other name
    AMARYL
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion

    Arm title
    		 Ertugliflozin 5 mg + Sitagliptin 100 mg
    Arm description
    		 Ertugliflozin 5 mg once daily, sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ertugliflozin
    Investigational medicinal product code
    Other name
    MK-8835, PF-04971729
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ertugliflozin 5 mg once daily for 52 weeks

    Investigational medicinal product name
    Sitagliptin
    Investigational medicinal product code
    Other name
    JANUVIA®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Sitagliptin 100 mg once daily, for 52 weeks

    Investigational medicinal product name
    Placebo to ertugliflozin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to ertugliflozin once daily for 52 weeks

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Glucophage Glucophage XR
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    For participants requiring metformin dose adjustment, metformin will be titrated over a period of up-to 4 weeks before the required dose-stabilization period (≥8 weeks) begins. While receiving blinded investigational product during the double-blind treatment period, participants will also receive metformin >= 1500 mg/day, tablets, oral, for 52 weeks.

    Investigational medicinal product name
    Insulin Glargine Rescue Medication
    Investigational medicinal product code
    Other name
    Lantus
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion

    Investigational medicinal product name
    Glimepiride Rescue Medication
    Investigational medicinal product code
    Other name
    AMARYL
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion

    Arm title
    		 Ertugliflozin 15 mg + Sitagliptin 100 mg
    Arm description
    		 Ertugliflozin 15 mg once daily, sitagliptin 100 mg once daily, and metformin >= 1500 mg/day, all for 52 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ertugliflozin
    Investigational medicinal product code
    Other name
    MK-8835, PF-04971729
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ertugliflozin 15 mg once daily, for 52 weeks

    Investigational medicinal product name
    Sitagliptin
    Investigational medicinal product code
    Other name
    JANUVIA®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Sitagliptin 100 mg once daily, for 52 weeks

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Glucophage Glucophage XR
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    For participants requiring metformin dose adjustment, metformin will be titrated over a period of up-to 4 weeks before the required dose-stabilization period (≥8 weeks) begins. While receiving blinded investigational product during the double-blind treatment period, participants will also receive metformin >= 1500 mg/day, tablets, oral, for 52 weeks.

    Investigational medicinal product name
    Insulin Glargine Rescue Medication
    Investigational medicinal product code
    Other name
    Lantus
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion

    Investigational medicinal product name
    Glimepiride Rescue Medication
    Investigational medicinal product code
    Other name
    AMARYL
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion

    Number of subjects in period 1
    		Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg
    Started
    250
    248
    247
    243
    245
    Treated
    250
    248
    247
    243
    244
    Completed
    226
    217
    219
    221
    218
    Not completed
    24
    31
    28
    22
    27
         Physician decision
    3
    -
    1
    2
    1
         Consent withdrawn by subject
    7
    11
    13
    9
    13
         Screen Failure
    -
    -
    -
    -
    1
         Non-Compliance with Study Drug
    2
    -
    -
    -
    1
         Adverse event, non-fatal
    3
    5
    2
    3
    2
         Death
    -
    1
    -
    -
    -
         Participant Moved
    1
    1
    1
    -
    2
         Lost to follow-up
    6
    12
    11
    5
    6
         Protocol deviation
    2
    1
    -
    3
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ertugliflozin 5 mg
    Reporting group description
    		 Ertugliflozin 5 mg once daily, placebo to ertugliflozin once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Ertugliflozin 15 mg
    Reporting group description
    		 Ertugliflozin 15 mg once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Sitagliptin 100 mg
    Reporting group description
    		 Sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Ertugliflozin 5 mg + Sitagliptin 100 mg
    Reporting group description
    		 Ertugliflozin 5 mg once daily, sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Ertugliflozin 15 mg + Sitagliptin 100 mg
    Reporting group description
    		 Ertugliflozin 15 mg once daily, sitagliptin 100 mg once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group values
    		 Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg Total
    Number of subjects
    		 250 248 247 243 245 1233
    Age Categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0
        Adults (18-64 years)
    		 214 205 205 199 211 1034
        From 65-84 years
    		 35 43 42 44 34 198
        85 years and over
    		 1 0 0 0 0 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 55.1 ± 10.1 55.3 ± 9.5 54.8 ± 10.7 55.2 ± 10.4 55.1 ± 9.8 -
    Gender Categorical
    Units: Subjects
        Female
    		 123 114 93 120 118 568
        Male
    		 127 134 154 123 127 665
    Baseline Hemoglobin A1C %
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). n=244, 247, 242, 237, 241
    Units: Percent glycated hemoglobin
        arithmetic mean (standard deviation)
    		 8.6 ± 1 8.6 ± 1 8.5 ± 1 8.6 ± 1 8.6 ± 1 -
    Baseline Fasting Plasma Glucose (FPG)
    Blood glucose was measured on a fasting basis after at least a 10-hour fast. n=250, 247, 246, 240, 241
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 184.1 ± 52.2 179.5 ± 45.6 177.4 ± 46.6 183.8 ± 44.3 177.2 ± 49.4 -
    Baseline Body Weight
    Units: Kilograms
        arithmetic mean (standard deviation)
    		 88.6 ± 22.2 88 ± 20.3 89.8 ± 23.4 89.5 ± 20.8 87.5 ± 20.5 -
    Baseline Beta-Cell Responsivity Static Component
    Beta-Cell Responsivity Static Component is a parameter used in assessing Beta-cell function. A frequently sampled 8-point MMTT was performed. Blood samples were collected before and after a standard meal and urine samples during the MMTT to measure urinary glucose excretion. Glucose, insulin, and C-peptide were analyzed in the blood samples. Analysis included both non-model-based [including insulinogenic index with C-peptide, glucose area under the curve (AUC)/insulin AUC] and model-based [beta cell function and insulin secretion rate at 9 mM glucose] testing. n= 58, 58, 55, 48, 50
    Units: 10^-9min^-1
        arithmetic mean (standard deviation)
    		 20.9 ± 26.1 18 ± 16.3 20.2 ± 21.2 20 ± 16.6 19.3 ± 21 -
    Baseline Sitting Systolic Blood Pressure
    Units: mm Hg
        arithmetic mean (standard deviation)
    		 129.7 ± 12.5 128.9 ± 12.5 128.3 ± 12.2 130.2 ± 12.6 129.1 ± 13.3 -
    Baseline Estimated Glomerular Filtration Rate, eGFR
    eGFR is a parameter used to assess kidney function. n =250, 248, 247, 242, 244
    Units: mL/min/1.73m^2
        arithmetic mean (standard deviation)
    		 91.9 ± 20.6 92.8 ± 21.4 92.6 ± 18.2 91.9 ± 20.4 92.6 ± 19.2 -

    End points

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    End points reporting groups
    Reporting group title
    Ertugliflozin 5 mg
    Reporting group description
    		 Ertugliflozin 5 mg once daily, placebo to ertugliflozin once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Ertugliflozin 15 mg
    Reporting group description
    		 Ertugliflozin 15 mg once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Sitagliptin 100 mg
    Reporting group description
    		 Sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Ertugliflozin 5 mg + Sitagliptin 100 mg
    Reporting group description
    		 Ertugliflozin 5 mg once daily, sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Ertugliflozin 15 mg + Sitagliptin 100 mg
    Reporting group description
    		 Ertugliflozin 15 mg once daily, sitagliptin 100 mg once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Subject analysis set title
    Ertugliflozin 5 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ertugliflozin 5 mg once daily, placebo to ertugliflozin once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Subject analysis set title
    Ertugliflozin 15 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ertugliflozin 15 mg once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Subject analysis set title
    Sitagliptin 100 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Subject analysis set title
    Ertugliflozin 5 mg + Sitagliptin 100 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ertugliflozin 5 mg once daily, sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Subject analysis set title
    Ertugliflozin 15 mg + Sitagliptin 100 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ertugliflozin 15 mg once daily, sitagliptin 100 mg once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Primary: Change from Baseline in Hemoglobin A1C (A1C) at Week 26 Excluding Data After Initiation of Rescue Therapy

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    End point title
    		 Change from Baseline in Hemoglobin A1C (A1C) at Week 26 Excluding Data After Initiation of Rescue Therapy
    End point description
    Hemoglobin A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (% glycated hemoglobin). This change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy. The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the A1C change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.
    End point type
    Primary
    End point timeframe
    Baseline and Week 26
    End point values
    		 Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects analysed
    250
    248
    247
    243
    244
    Units: Percent glycated hemoglobin
        least squares mean (confidence interval 95%)
    -1.02 (-1.14 to -0.9)
    -1.08 (-1.2 to -0.96)
    -1.05 (-1.17 to -0.93)
    -1.49 (-1.61 to -1.36)
    -1.52 (-1.64 to -1.4)
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on Constrained Longitudinal Data Analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Ertugliflozin 5 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    493
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.63
         upper limit
    		 -0.3
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 -0.27
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Ertugliflozin 15 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    492
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.61
         upper limit
    		 -0.27
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.63
         upper limit
    		 -0.3

    Primary: Percentage of Participants Who Experienced an Adverse Event (AE)

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    End point title
    		 Percentage of Participants Who Experienced an Adverse Event (AE)
    End point description
    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The population analyzed included all randomized, treated participants.
    End point type
    Primary
    End point timeframe
    Up to 54 weeks
    End point values
    		 Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects analysed
    250
    248
    247
    243
    244
    Units: Percentage of Participants
        number (not applicable)
    62
    57.7
    57.5
    58.8
    55.7
    Statistical analysis title
    		 Difference in % of Participants
    Statistical analysis description
    Difference in % of Participants
    Comparison groups
    Ertugliflozin 5 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    493
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in % vs Ertugliflozin 5 mg
    Point estimate
    -3.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.7
         upper limit
    		 5.5
    Statistical analysis title
    		 Difference in % vs Ertugliflozin 15 mg
    Statistical analysis description
    Difference in % vs Ertugliflozin 15 mg
    Comparison groups
    Ertugliflozin 15 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    492
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in % vs Ertugliflozin 5 mg
    Point estimate
    -1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.6
         upper limit
    		 6.8
    Statistical analysis title
    		 Difference in % vs Sitagliptin 100 mg
    Statistical analysis description
    Difference in % vs Sitagliptin 100 mg
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in % vs Sitagliptin 100 mg
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.4
         upper limit
    		 10.1
    Statistical analysis title
    		 Difference in % vs Sitagliptin 100 mg
    Statistical analysis description
    Difference in % vs Sitagliptin 100 mg
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in % vs Sitagliptin 100 mg
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.5
         upper limit
    		 7

    Primary: Percentage of Participants Who Discontinued Study Medication due to an AE

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    End point title
    		 Percentage of Participants Who Discontinued Study Medication due to an AE
    End point description
    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The population analyzed included all randomized, treated participants.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects analysed
    250
    248
    247
    243
    244
    Units: Percentage of Participants
        number (not applicable)
    3.2
    3.2
    2.8
    3.3
    3.7
    Statistical analysis title
    		 Difference in % of Participants
    Statistical analysis description
    Difference in % of Participants
    Comparison groups
    Ertugliflozin 5 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    493
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in % vs Ertugliflozin 5 mg
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 3.6
    Statistical analysis title
    		 Difference in % of Participants
    Statistical analysis description
    Difference in % of Participants
    Comparison groups
    Ertugliflozin 15 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    492
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in % vs Ertugliflozin 15 mg
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 4
    Statistical analysis title
    		 Difference in % of Participants
    Statistical analysis description
    Difference in % of Participants
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in % vs Sitagliptin 100 mg
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 3.9
    Statistical analysis title
    		 Difference in % of Participants
    Statistical analysis description
    Difference in % of Participants
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in % vs Sitagliptin 100 mg
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.5
         upper limit
    		 4.4

    Secondary: Change from Baseline in Body Weight at Week 26 Excluding Data After Initiation of Rescue Therapy

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    End point title
    		 Change from Baseline in Body Weight at Week 26 Excluding Data After Initiation of Rescue Therapy
    End point description
    The change in body weight from baseline reflects the Week 26 body weight minus the Week 0 body weight. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy. The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the body weight change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 26
    End point values
    		 Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects analysed
    250
    248
    247
    243
    244
    Units: kilograms
        least squares mean (confidence interval 95%)
    -2.69 (-3.13 to -2.25)
    -3.74 (-4.18 to -3.29)
    -0.67 (-1.12 to -0.22)
    -2.52 (-2.97 to -2.07)
    -2.94 (-3.39 to -2.49)
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -1.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.48
         upper limit
    		 -1.22
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -2.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 -1.64

    Secondary: Change from Baseline in Fasting Plasma Glucose (FPG) at Week 26 Excluding Data After Initiation of Rescue Therapy

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    End point title
    		 Change from Baseline in Fasting Plasma Glucose (FPG) at Week 26 Excluding Data After Initiation of Rescue Therapy
    End point description
    Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 26 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 26 minus FPG at baseline). Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy. The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the FPG change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 26
    End point values
    		 Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects analysed
    250
    248
    247
    243
    244
    Units: mg/dL
        least squares mean (confidence interval 95%)
    -35.73 (-40.04 to -31.42)
    -36.91 (-41.21 to -32.62)
    -25.56 (-29.93 to -21.19)
    -43.96 (-48.29 to -39.63)
    -48.7 (-53.01 to -44.39)
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Ertugliflozin 5 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    493
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.004
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -8.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.82
         upper limit
    		 -2.65
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -18.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.03
         upper limit
    		 -12.77
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Ertugliflozin 15 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    492
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -11.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.35
         upper limit
    		 -6.23
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -23.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.76
         upper limit
    		 -17.53

    Secondary: Change from Baseline in Sitting Systolic Blood Pressure at Week 26 Excluding Data After Initiation of Rescue Therapy

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    End point title
    		 Change from Baseline in Sitting Systolic Blood Pressure at Week 26 Excluding Data After Initiation of Rescue Therapy
    End point description
    This change from baseline reflects the Week 26 sitting systolic blood pressure (SBP) minus the Week 0 sitting SBP. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy. The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the systolic blood pressure change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 26
    End point values
    		 Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects analysed
    250
    248
    247
    243
    244
    Units: mmHg
        least squares mean (confidence interval 95%)
    -3.89 (-5.28 to -2.5)
    -3.69 (-5.08 to -2.3)
    -0.66 (-2.07 to 0.76)
    -3.42 (-4.82 to -2.03)
    -3.67 (-5.06 to -2.29)
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.005
    Method
    		 Constrained Longitudinal Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -2.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.69
         upper limit
    		 -0.83
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.002
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -3.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.94
         upper limit
    		 -1.09

    Secondary: Percentage of Participants Achieving a Hemoglobin A1C of <7% (Raw Proportions) at Week 26 Excluding Data After Initiation of Rescue Therapy

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    End point title
    		 Percentage of Participants Achieving a Hemoglobin A1C of <7% (Raw Proportions) at Week 26 Excluding Data After Initiation of Rescue Therapy
    End point description
    Hemoglobin A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy. The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a post-randomization measurement for the A1C change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects analysed
    250
    248
    247
    243
    244
    Units: Percent
        number (not applicable)
    26.4
    31.9
    32.8
    52.3
    49.2
    Statistical analysis title
    		 Odds Ratio
    Statistical analysis description
    Logistic regression with multiple imputations based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Ertugliflozin 5 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    493
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.68
         upper limit
    		 6.4
    Statistical analysis title
    		 Odds Ratio
    Statistical analysis description
    Logistic regression with multiple imputations based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Ertugliflozin 15 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    492
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.68
         upper limit
    		 3.83
    Statistical analysis title
    		 Odds Ratio
    Statistical analysis description
    Logistic regression with multiple imputations based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.92
         upper limit
    		 4.54
    Statistical analysis title
    		 Odds Ratio
    Statistical analysis description
    Logistic regression with multiple imputations based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.69
         upper limit
    		 3.89

    Secondary: Change from Baseline in β-cell Responsivity Static Component (Φs) (10-9min-1) From the 8-Point Meal Tolerance Test (MMTT at Week 26

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    End point title
    		 Change from Baseline in β-cell Responsivity Static Component (Φs) (10-9min-1) From the 8-Point Meal Tolerance Test (MMTT at Week 26
    End point description
    Measurements of plasma glucose, insulin and C-peptide collected, and urine samples were used to assess parameters of insulin sensitivity and β-cell function. The analysis model parameters, i.e. α, β, k, (and h) were estimated in Simulation, Analysis, and Modeling Software for tracer and pharmacokinetic studies (SAAM II) using least squares approach. The endpoint Φs (β-cell responsivity static component) is a function of α and is calculated inside SAAM II, by specifying the formula in the Equation section of the STU file: - Φs = β /0.05551, the unit is 10-9^min-1. A higher number indicates greater β-cell responsivity. The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the beta-cell responsivity static component change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 26, 30 minutes before and immediately prior to administration of the standard meal and 15, 30, 60, 90, 120 and 180 minutes following the start of the administration of the meal
    End point values
    		 Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects analysed
    66
    67
    63
    55
    61
    Units: 10^-9 min^-1
        least squares mean (confidence interval 95%)
    8.62 (1.28 to 15.96)
    9.71 (2.29 to 17.13)
    21.11 (13.55 to 28.67)
    16.24 (8.36 to 24.11)
    11.51 (3.76 to 19.26)
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Ertugliflozin 5 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.155
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    7.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 18.13
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Ertugliflozin 15 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.734
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    1.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.66
         upper limit
    		 12.27
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 5 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.369
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -4.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.54
         upper limit
    		 5.8
    Statistical analysis title
    		 Difference in the Least Squares Means
    Statistical analysis description
    Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment. Time was treated as a categorical variable.
    Comparison groups
    Sitagliptin 100 mg v Ertugliflozin 15 mg + Sitagliptin 100 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.075
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in the Least Squares Means
    Point estimate
    -9.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.17
         upper limit
    		 0.98

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 54 weeks
    Adverse event reporting additional description
    The safety population consisted of all randomized participants who took at least one dose of trial treatment. Participants were included in the treatment group corresponding to the trial treatment they actually took for the analysis of safety data. This analysis included events that occurred following the initiation of rescue therapy.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Ertugliflozin 15 mg
    Reporting group description
    		 Ertugliflozin 15 mg once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Ertugliflozin 5 mg
    Reporting group description
    		 Ertugliflozin 5 mg once daily, placebo to ertugliflozin once daily, placebo to sitagliptin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Ertugliflozin 5 mg + Sitagliptin 100 mg
    Reporting group description
    		 Ertugliflozin 5 mg once daily, sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Ertugliflozin 15 mg + Sitagliptin 100 mg
    Reporting group description
    		 Ertugliflozin 15 mg once daily, sitagliptin 100 mg once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Reporting group title
    Sitagliptin 100 mg
    Reporting group description
    		 Sitagliptin 100 mg once daily, placebo to ertugliflozin once daily, and metformin >= 1500 mg/day, all for 52 weeks

    Serious adverse events
    		 Ertugliflozin 15 mg Ertugliflozin 5 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg Sitagliptin 100 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 248 (2.02%)
    12 / 250 (4.80%)
    9 / 243 (3.70%)
    12 / 244 (4.92%)
    9 / 247 (3.64%)
         number of deaths (all causes)
    1
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Nodal marginal zone B-cell lymphoma stage III
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pancreatic neoplasm
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 248 (0.40%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 248 (0.40%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood potassium decreased
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood sodium decreased
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Joint injury
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Overdose
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    2 / 244 (0.82%)
    2 / 247 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Atrial fibrillation
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Microvascular coronary artery disease
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    1 / 244 (0.41%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    1 / 248 (0.40%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 248 (0.40%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 248 (0.40%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral hernia
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 248 (0.00%)
    1 / 250 (0.40%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 248 (0.00%)
    2 / 250 (0.80%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Cholecystitis chronic
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Cholelithiasis
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Cellulitis orbital
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    1 / 248 (0.40%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    0 / 244 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Pneumonia
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Pyelonephritis acute
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    0 / 243 (0.00%)
    1 / 244 (0.41%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    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
    Obesity
         subjects affected / exposed
    0 / 248 (0.00%)
    0 / 250 (0.00%)
    1 / 243 (0.41%)
    0 / 244 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ertugliflozin 15 mg Ertugliflozin 5 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg Sitagliptin 100 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    43 / 248 (17.34%)
    36 / 250 (14.40%)
    31 / 243 (12.76%)
    38 / 244 (15.57%)
    28 / 247 (11.34%)
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    13 / 248 (5.24%)
    6 / 250 (2.40%)
    12 / 243 (4.94%)
    12 / 244 (4.92%)
    6 / 247 (2.43%)
         occurrences all number
    14
    6
    14
    13
    7
    Urinary tract infection
         subjects affected / exposed
    19 / 248 (7.66%)
    20 / 250 (8.00%)
    14 / 243 (5.76%)
    8 / 244 (3.28%)
    13 / 247 (5.26%)
         occurrences all number
    23
    24
    18
    12
    13
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    13 / 248 (5.24%)
    12 / 250 (4.80%)
    9 / 243 (3.70%)
    20 / 244 (8.20%)
    11 / 247 (4.45%)
         occurrences all number
    29
    25
    17
    42
    22

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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