Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Diet and Exercise (MK-8835-017)

• ClinicalTrials.gov Identifier: NCT02226003
• Recruitment Status: Completed
• First Posted: August 26, 2014
• Results First Posted: April 7, 2017
• Last Update Posted: September 13, 2018
• Sponsor: Merck Sharp & Dohme LLC
• Collaborator: Pfizer
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Type 2 Diabetes Mellitus
• Interventions: Drug: Ertugliflozin; Drug: Sitagliptin; Drug: Placebo to Ertugliflozin; Drug: Placebo to Sitagliptin; Drug: Glimepiride
• Enrollment: 291

Participant Flow

Recruitment Details	A total of 96 sites received independent ethics committees/institutional review boards' approval and 66 sites in 9 countries enrolled at least 1 participant.
Pre-assignment Details	The study included a 1-week screening period; an 8-week (or greater) antihyperglycemic agent (AHA) wash-off period; and a 2-week single-blind placebo run-in period.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Period Title: Overall Study
Started	98	96	97
Completed	96	95	91
Not Completed	2	1	6
Reason Not Completed
Lost to Follow-up	2	1	3
Withdrawal by Subject	0	0	3

Baseline Characteristics

Arm/Group Title		Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo	Total
Arm/Group Description		Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		98	96	97	291
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	98 participants	96 participants	97 participants	291 participants
		56.4 (9.3)	56.1 (10.1)	54.3 (10.3)	55.6 (10.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	98 participants	96 participants	97 participants	291 participants
	Female	41 41.8%	43 44.8%	40 41.2%	124 42.6%
	Male	57 58.2%	53 55.2%	57 58.8%	167 57.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1C (HbA1C) at Week 26 - Full Analysis Set (FAS Population Excluding Rescue Approach
Description	HbA1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). HbA1C represents the percentage of glycated hemoglobin. A negative number indicates a reduction in HbA1C level. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

FAS population includes randomized participants who took at least 1 dose of study medication and had at least one assessment at or after baseline for the change from baseline in the Week 26 HbA1C endpoint.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description:	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Overall Number of Participants Analyzed	98	96	96
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage
	-1.60; (-1.82 to -1.39)	-1.68; (-1.90 to -1.46)	-0.44; (-0.69 to -0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.16
	Confidence Interval	(2-Sided) 95%; -1.49 to -0.84
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.24
	Confidence Interval	(2-Sided) 95%; -1.57 to -0.91
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants as Treated Excluding Rescue Approach
Description	An adverse event (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. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
Time Frame	Up to Week 28

Outcome Measure Data

Analysis Population Description

All Subjects as Treated (ASaT) population consisted of all randomized participants who received at least one dose of a study drug.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description:	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Overall Number of Participants Analyzed	98	96	97
Measure Type: Number; Unit of Measure: Percentage of Participants
	44.9	44.8	42.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentage vs Placebo
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; -11.2 to 16.4
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentage vs Placebo
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; -11.4 to 16.4
	Estimation Comments	[Not Specified]

3. Primary Outcome

Title	Percentage of Participants Who Discontinued Study Medication Due to an AE - All Participants as Treated Excluding Rescue Approach
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. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
Time Frame	Up to Week 26

Outcome Measure Data

Analysis Population Description

ASaT population consisted of all randomized participants who received at least one dose of a study drug.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description:	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Overall Number of Participants Analyzed	98	96	97
Measure Type: Number; Unit of Measure: Percentage of Participants
	2.0	2.1	2.1

4. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 - Full Analysis Set Excluding Rescue Approach
Description	Blood glucose was measured after a ≥10 hour fast. 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 rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

FAS population includes randomized participants who took at least 1 dose of study medication and had at least one assessment at or after baseline for the change from baseline in the Week 26 FPG endpoint.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description:	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Overall Number of Participants Analyzed	98	96	96
Least Squares Mean (95% Confidence Interval); Unit of Measure: milligrams/deciliter
	-48.25; (-56.12 to -40.38)	-55.36; (-63.29 to -47.42)	-9.30; (-18.58 to -0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-38.94
	Confidence Interval	(2-Sided) 95%; -49.93 to -27.96
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-46.05
	Confidence Interval	(2-Sided) 95%; -57.09 to -35.02
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change From Baseline in 2-hour Post-Meal Glucose (PMG) at Week 26 - Full Analysis Set Excluding Rescue Approach
Description	Change from baseline at Week 26 is defined as 2-hour PMG at Week 26 minus 2-hour PMG at Week 0. Two-hour post-meal glucose was measured following a standard meal. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

FAS population is all randomized participants who took at least 1 dose of study medication and had at least one assessment at or after baseline for the change from baseline in the Week 26 2-hour PMG endpoint.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description:	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Overall Number of Participants Analyzed	97	95	91
Least Squares Mean (95% Confidence Interval); Unit of Measure: milligrams/deciliter
	-82.80; (-95.96 to -69.64)	-90.03; (-103.34 to -76.71)	-20.38; (-35.62 to -5.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-62.42
	Confidence Interval	(2-Sided) 95%; -80.47 to -44.37
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-69.65
	Confidence Interval	(2-Sided) 95%; -87.83 to -51.46
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants With HbA1C <7% (<53 mmol/Mol) at Week 26
Description	HbA1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). HbA1c represents the percentage of glycated hemoglobin.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS population includes randomized participants who took at least 1 dose of study medication and had at least one assessment at or after baseline in the Week 26 HbA1C endpoint.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description:	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Overall Number of Participants Analyzed	98	96	96
Measure Type: Number; Unit of Measure: Percentage of participants
	35.7	31.3	8.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Logistic regression model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.88
	Confidence Interval	(2-Sided) 95%; 2.81 to 16.83
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Logistic regression model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.39
	Confidence Interval	(2-Sided) 95%; 2.98 to 18.31
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 26 - Full Analysis Set Excluding Rescue Approach
Description	Body weight was measured using a standardized, digital scale at each of the pre-defined nominal time points. Weight was taken in duplicate throughout the trial at approximately the same time of day, after voiding (i.e., forced void) and while wearing only a gown and underwear. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

FAS population is all randomized participants who took at least 1 dose of study medication and had at least one assessment at or after baseline for the change from baseline in the Week 26 body weight endpoint.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description:	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Overall Number of Participants Analyzed	98	96	97
Least Squares Mean (95% Confidence Interval); Unit of Measure: Kilograms
	-2.94; (-3.60 to -2.28)	-3.04; (-3.71 to -2.38)	-0.94; (-1.70 to -0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95%; -2.99 to -1.01
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.10
	Confidence Interval	(2-Sided) 95%; -3.10 to -1.11
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure at Week 26 - Full Analysis Set Excluding Rescue Approach
Description	Blood pressure measurements were taken after at least 5 minutes of rest. Three measurements were taken approximately 2 minutes apart with the triplicate set recorded. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants who took at least 1 dose of study medication and had at least one assessment at or after baseline for the change from baseline in the Week 26 sitting systolic blood pressure endpoint.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description:	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Overall Number of Participants Analyzed	98	96	97
Least Squares Mean (95% Confidence Interval); Unit of Measure: millimeters of mercury
	-2.04; (-4.23 to 0.16)	-3.98; (-6.19 to -1.78)	2.41; (-0.34 to 5.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.011
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-4.44
	Confidence Interval	(2-Sided) 95%; -7.87 to -1.01
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-6.39
	Confidence Interval	(2-Sided) 95%; -9.83 to -2.95
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 - Full Analysis Set Excluding Rescue Approach
Description	Blood pressure measurements were taken after at least 5 minutes of rest. Three measurements were taken approximately 2 minutes apart with the triplicate set recorded. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

The FAS population included all randomized participants who took at least 1 dose of study medication and had at least one assessment at or after baseline for the change from baseline in the Week 26 sitting diastolic blood pressure endpoint.

Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + Sitagliptin 100 mg	Placebo
Arm/Group Description:	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.	Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.	Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Overall Number of Participants Analyzed	98	96	97
Least Squares Mean (95% Confidence Interval); Unit of Measure: millimeters of mercury
	-0.44; (-1.99 to 1.11)	-0.97; (-2.52 to 0.59)	1.21; (-0.73 to 3.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.184
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.65
	Confidence Interval	(2-Sided) 95%; -4.09 to 0.79
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg + Sitagliptin 100 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.080
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.18
	Confidence Interval	(2-Sided) 95%; -4.62 to 0.26
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Up to Week 28
Adverse Event Reporting Description	The serious adverse event table includes events after the initiation of glycemic rescue. The non-serious adverse event table excludes events after the initiation of glycemic rescue.
Arm/Group Title	Ertugliflozin 5 mg + Sitagliptin 100 mg		Ertugliflozin 15 mg + Sitagliptin 100 mg		Placebo
Arm/Group Description	Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.		Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.		Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
All-Cause Mortality
	Ertugliflozin 5 mg + Sitagliptin 100 mg		Ertugliflozin 15 mg + Sitagliptin 100 mg		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Ertugliflozin 5 mg + Sitagliptin 100 mg		Ertugliflozin 15 mg + Sitagliptin 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/98 (2.04%)		3/96 (3.13%)		5/97 (5.15%)
Immune system disorders
Allergy to arthropod sting † 1	0/98 (0.00%)	0	1/96 (1.04%)	1	0/97 (0.00%)	0
Infections and infestations
Appendicitis † 1	0/98 (0.00%)	0	0/96 (0.00%)	0	1/97 (1.03%)	1
Cellulitis staphylococcal † 1	0/98 (0.00%)	0	0/96 (0.00%)	0	1/97 (1.03%)	1
Peritonitis † 1	0/98 (0.00%)	0	0/96 (0.00%)	0	1/97 (1.03%)	1
Urinary tract infection † 1	0/98 (0.00%)	0	1/96 (1.04%)	1	0/97 (0.00%)	0
Injury, poisoning and procedural complications
Multiple fractures † 1	0/98 (0.00%)	0	0/96 (0.00%)	0	1/97 (1.03%)	1
Toxicity to various agents † 1	1/98 (1.02%)	1	0/96 (0.00%)	0	0/97 (0.00%)	0
Musculoskeletal and connective tissue disorders
Spinal column stenosis † 1	1/98 (1.02%)	1	0/96 (0.00%)	0	0/97 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma † 1	0/98 (0.00%)	0	1/96 (1.04%)	1	0/97 (0.00%)	0
Nervous system disorders
Ischaemic stroke † 1	0/98 (0.00%)	0	0/96 (0.00%)	0	1/97 (1.03%)	1
Renal and urinary disorders
Nephrolithiasis † 1	0/98 (0.00%)	0	0/96 (0.00%)	0	1/97 (1.03%)	1
Skin and subcutaneous tissue disorders
Angioedema † 1	0/98 (0.00%)	0	0/96 (0.00%)	0	1/97 (1.03%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Ertugliflozin 5 mg + Sitagliptin 100 mg		Ertugliflozin 15 mg + Sitagliptin 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/98 (8.16%)		3/96 (3.13%)		12/97 (12.37%)
Infections and infestations
Urinary tract infection † 1	5/98 (5.10%)	6	2/96 (2.08%)	2	1/97 (1.03%)	1
Investigations
Blood glucose increased † 1	3/98 (3.06%)	4	0/96 (0.00%)	0	7/97 (7.22%)	14
Metabolism and nutrition disorders
Hyperglycaemia † 1	0/98 (0.00%)	0	1/96 (1.04%)	1	6/97 (6.19%)	6
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Miller S, Krumins T, Zhou H, Huyck S, Johnson J, Golm G, Terra SG, Mancuso JP, Engel SS, Lauring B. Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study. Diabetes Ther. 2018 Feb;9(1):253-268. doi: 10.1007/s13300-017-0358-0. Epub 2018 Jan 8.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gallo S, Raji A, Calle RA, Pong A, Meyer C. The effects of ertugliflozin on beta-cell function: Pooled analysis from four phase 3 randomized controlled studies. Diabetes Obes Metab. 2020 Dec;22(12):2267-2275. doi: 10.1111/dom.14149. Epub 2020 Aug 27.

Gallo S, Calle RA, Terra SG, Pong A, Tarasenko L, Raji A. Effects of Ertugliflozin on Liver Enzymes in Patients with Type 2 Diabetes: A Post-Hoc Pooled Analysis of Phase 3 Trials. Diabetes Ther. 2020 Aug;11(8):1849-1860. doi: 10.1007/s13300-020-00867-1. Epub 2020 Jul 9.

Patel S, Hickman A, Frederich R, Johnson S, Huyck S, Mancuso JP, Gantz I, Terra SG. Safety of Ertugliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Seven Phase 3 Randomized Controlled Trials. Diabetes Ther. 2020 Jun;11(6):1347-1367. doi: 10.1007/s13300-020-00803-3. Epub 2020 May 5.

Liu J, Tarasenko L, Pong A, Huyck S, Wu L, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Efficacy and safety of ertugliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Aug;36(8):1277-1284. doi: 10.1080/03007995.2020.1760228. Epub 2020 May 13.

Liu J, Tarasenko L, Pong A, Huyck S, Patel S, Hickman A, Mancuso JP, Ellison MC, Gantz I, Terra SG. Efficacy and safety of ertugliflozin in Hispanic/Latino patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Jul;36(7):1097-1106. doi: 10.1080/03007995.2020.1760227. Epub 2020 May 13.

Liu J, Patel S, Cater NB, Wu L, Huyck S, Terra SG, Hickman A, Darekar A, Pong A, Gantz I. Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2020 Apr;22(4):574-582. doi: 10.1111/dom.13931. Epub 2020 Jan 3.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02226003
• Other Study ID Numbers: 8835-017; 2014-001049-25 ( EudraCT Number ); B1521047 ( Other Identifier: Pfizer Protocol Number )
• First Submitted: August 25, 2014
• First Posted: August 26, 2014
• Results First Submitted: February 23, 2017
• Results First Posted: April 7, 2017
• Last Update Posted: September 13, 2018