Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Ertugliflozin in Asian Participants With Type 2 Diabetes and Inadequate Glycemic Control on Metformin Monotherapy (MK-8835-012) (NCT NCT02630706)

NCT ID: NCT02630706

Last Updated: 2018-12-07

Results Overview

A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 506 participants
• Primary outcome timeframe: Baseline and Week 26
• Results posted on: 2018-12-07

Participant Flow

In total, 1078 participants were screened, and 506 participants were randomized at 50 sites in China, Hong Kong, Republic of Korea, the Philippines, and Taiwan.

Participant milestones

Measure	Ertugliflozin 5 mg Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Overall Study STARTED	170	169	167
Overall Study Treated	170	169	167
Overall Study COMPLETED	163	160	157
Overall Study NOT COMPLETED	7	9	10

Reasons for withdrawal

Measure	Ertugliflozin 5 mg Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Overall Study Adverse Event	2	1	1
Overall Study Lost to Follow-up	0	1	2
Overall Study Physician Decision	1	1	0
Overall Study Pregnancy	0	1	0
Overall Study Withdrawal by Subject	4	5	7

Baseline Characteristics

The analysis population included all randomized participants who received at least one dose of investigational product.

Baseline characteristics by cohort

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Total n=506 Participants Total of all reporting groups
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) Black or African American	0 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Age, Continuous	56.1 Years STANDARD_DEVIATION 9.0 • n=170 Participants	56.3 Years STANDARD_DEVIATION 9.3 • n=169 Participants	56.9 Years STANDARD_DEVIATION 9.0 • n=167 Participants	56.5 Years STANDARD_DEVIATION 9.1 • n=506 Participants
Sex: Female, Male Female	75 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	71 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	79 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	225 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Sex: Female, Male Male	95 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	98 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	88 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	281 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) Asian	170 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	169 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	167 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	506 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) White	0 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) More than one race	0 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	0 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Body Weight	71.4 Kilograms STANDARD_DEVIATION 11.1 • n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	69.5 Kilograms STANDARD_DEVIATION 10.9 • n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	70.1 Kilograms STANDARD_DEVIATION 12.4 • n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	70.3 Kilograms STANDARD_DEVIATION 11.5 • n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Baseline Hemoglobin A1C (A1C)	8.14 Percentage A1C STANDARD_DEVIATION 0.89 • n=169 Participants • The analysis population included all randomized participants who have received at least one dose of investigational product and had a baseline A1C measurement.	8.09 Percentage A1C STANDARD_DEVIATION 0.91 • n=169 Participants • The analysis population included all randomized participants who have received at least one dose of investigational product and had a baseline A1C measurement.	8.13 Percentage A1C STANDARD_DEVIATION 0.96 • n=166 Participants • The analysis population included all randomized participants who have received at least one dose of investigational product and had a baseline A1C measurement.	8.12 Percentage A1C STANDARD_DEVIATION 0.92 • n=504 Participants • The analysis population included all randomized participants who have received at least one dose of investigational product and had a baseline A1C measurement.
Baseline Fasting Plasma Glucose (FPG)	170.1 mg/dL STANDARD_DEVIATION 36.0 • n=167 Participants • The analysis population included all randomized participants who have received at least one dose of investigational product and had a baseline FPG measurement.	167.3 mg/dL STANDARD_DEVIATION 41.1 • n=168 Participants • The analysis population included all randomized participants who have received at least one dose of investigational product and had a baseline FPG measurement.	165.8 mg/dL STANDARD_DEVIATION 37.6 • n=166 Participants • The analysis population included all randomized participants who have received at least one dose of investigational product and had a baseline FPG measurement.	167.8 mg/dL STANDARD_DEVIATION 38.3 • n=501 Participants • The analysis population included all randomized participants who have received at least one dose of investigational product and had a baseline FPG measurement.
Baseline estimated glomerular filtration rate (eGFR)	97.9 mL/min/1.73 m^2 STANDARD_DEVIATION 19.2 • n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	100.2 mL/min/1.73 m^2 STANDARD_DEVIATION 19.8 • n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	99.9 mL/min/1.73 m^2 STANDARD_DEVIATION 20.2 • n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	99.3 mL/min/1.73 m^2 STANDARD_DEVIATION 19.7 • n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Country China	136 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	135 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	135 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	406 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Country Hong Kong	10 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	10 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	7 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	27 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Country Korea, Republic of	13 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	10 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	9 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	32 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Country Philippines	7 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	8 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	8 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	23 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Country Taiwan	4 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	6 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	8 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	18 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Anti-hyperglycemic Agent (AHA) Status at Screening (Metformin Alone OR Metformin + Another AHA) Metformin alone	111 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	121 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	121 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	353 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Anti-hyperglycemic Agent (AHA) Status at Screening (Metformin Alone OR Metformin + Another AHA) Metformin + Another AHA	59 Participants n=170 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	48 Participants n=169 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	46 Participants n=167 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.	153 Participants n=506 Participants • The analysis population included all randomized participants who received at least one dose of investigational product.
Gender (China Substudy) Female	65 Participants n=136 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	51 Participants n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	66 Participants n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	182 Participants n=406 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.
Gender (China Substudy) Male	71 Participants n=136 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	84 Participants n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	69 Participants n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	224 Participants n=406 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.
Age Continuous (China Substudy)	56.0 Years STANDARD_DEVIATION 9.0 • n=136 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	56.2 Years STANDARD_DEVIATION 9.4 • n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	56.8 Years STANDARD_DEVIATION 8.6 • n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	56.3 Years STANDARD_DEVIATION 9.0 • n=406 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.
Body Weight (China Substudy)	71.4 Kilograms STANDARD_DEVIATION 11.1 • n=136 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	70.2 Kilograms STANDARD_DEVIATION 10.2 • n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	70.6 Kilograms STANDARD_DEVIATION 12.2 • n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	70.7 Kilograms STANDARD_DEVIATION 11.2 • n=406 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.
Baseline A1C (China Substudy)	8.22 Percentage A1C STANDARD_DEVIATION 0.94 • n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product and had a baseline A1C measurement.	8.13 Percentage A1C STANDARD_DEVIATION 0.96 • n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product and had a baseline A1C measurement.	8.09 Percentage A1C STANDARD_DEVIATION 0.98 • n=134 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product and had a baseline A1C measurement.	8.14 Percentage A1C STANDARD_DEVIATION 0.96 • n=404 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product and had a baseline A1C measurement.
Baseline FPG (China Substudy)	175.7 mg/dL STANDARD_DEVIATION 36.2 • n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product and had a baseline FPG measurement.	170.5 mg/dL STANDARD_DEVIATION 43.0 • n=134 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product and had a baseline FPG measurement.	165.5 mg/dL STANDARD_DEVIATION 37.9 • n=134 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product and had a baseline FPG measurement.	170.6 mg/dL STANDARD_DEVIATION 39.3 • n=403 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product and had a baseline FPG measurement.
Baseline eGFR (China Substudy)	99.8 mL/min/1.73 m^2 STANDARD_DEVIATION 19.0 • n=136 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	102.7 mL/min/1.73 m^2 STANDARD_DEVIATION 19.8 • n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	100.8 mL/min/1.73 m^2 STANDARD_DEVIATION 21.1 • n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	101.1 mL/min/1.73 m^2 STANDARD_DEVIATION 19.9 • n=406 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.
Anti-AHA status at Screening (Metformin Alone OR Metformin + Another AHA) (China Substudy) Metformin Alone	85 Participants n=136 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	92 Participants n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	93 Participants n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	270 Participants n=406 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.
Anti-AHA status at Screening (Metformin Alone OR Metformin + Another AHA) (China Substudy) Metformin + Another AHA	51 Participants n=136 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	43 Participants n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	42 Participants n=135 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.	136 Participants n=406 Participants • The analysis population included all randomized participants in China who received at least one dose of investigational product.

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in A1C (%) at Week 26 (Excluding Rescue Approach)	-1.00 Percentage A1C Interval -1.12 to -0.88	-0.89 Percentage A1C Interval -1.01 to -0.77	-0.20 Percentage A1C Interval -0.33 to -0.08

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in A1C (%) at Week 26 (Excluding Rescue Approach) (China Subpopulation)	-1.01 Percentage A1C Interval -1.14 to -0.87	-0.92 Percentage A1C Interval -1.05 to -0.79	-0.24 Percentage A1C Interval -0.38 to -0.1

PRIMARY outcome

Timeframe: Up to 28 weeks

Population: The analysis population included all randomized participants who received at least one dose of investigational product.

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.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach)	56.5 Percentage of participants	53.3 Percentage of participants	59.3 Percentage of participants

PRIMARY outcome

Timeframe: Up to 28 weeks

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product .

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.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach) (China Subpopulation)	54.4 Percentage of participants	50.4 Percentage of participants	59.3 Percentage of participants

PRIMARY outcome

Timeframe: Up to 26 weeks

Population: The analysis population included all randomized participants who received at least one dose of investigational product.

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.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach)	1.2 Percentage of Participants	0.6 Percentage of Participants	1.8 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 26 weeks

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product.

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.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach) (China Subpopulation)	0.7 Percentage of Participants	0.7 Percentage of Participants	2.2 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.

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 Week 0) which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach)	-37.09 mg/dL Interval -41.73 to -32.45	-34.47 mg/dL Interval -39.15 to -29.79	-6.69 mg/dL Interval -11.57 to -1.82

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.

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 Week 0) which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach) (China Subpopulation)	-39.01 mg/dL Interval -43.87 to -34.15	-36.67 mg/dL Interval -41.64 to -31.71	-10.46 mg/dL Interval -15.61 to -5.31

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants and who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.

The change in body weight from baseline reflects the Week 26 body weight minus the Week 0 body weight (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach)	-2.95 Kilograms Interval -3.29 to -2.6	-3.18 Kilograms Interval -3.52 to -2.83	-1.17 Kilograms Interval -1.54 to -0.81

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.

The change in body weight from baseline reflects the Week 26 body weight minus the Week 0 body weight (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach) (China Subpopulation)	-3.11 Kilograms Interval -3.5 to -2.72	-3.38 Kilograms Interval -3.78 to -2.98	-1.33 Kilograms Interval -1.75 to -0.91

SECONDARY outcome

Timeframe: Week 26

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants With HbA1c of <7.0% (53 mmol/Mol) (Logistic Regression Using Multiple Imputation Based on cLDA Model: Excluding Rescue Approach)	38.2 Percentage of participants	40.8 Percentage of participants	16.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 26

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants With HbA1c of <7.0% (53 mmol/Mol) (Logistic Regression Using Multiple Imputation Based on cLDA Model: Excluding Rescue Approach) (China Subpopulation)	35.3 Percentage of participants	42.2 Percentage of participants	18.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

This change from baseline reflects the Week 26 sitting systolic blood pressure (SBP) minus the Week 0 sitting SBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach)	-5.09 mmHg Interval -6.78 to -3.4	-3.87 mmHg Interval -5.58 to -2.16	0.22 mmHg Interval -1.58 to 2.01

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

This change from baseline reflects the Week 26 sitting systolic blood pressure (SBP) minus the Week 0 sitting SBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach) (China Subpopulation)	-5.64 mmHg Interval -7.53 to -3.75	-4.19 mmHg Interval -6.14 to -2.25	-1.56 mmHg Interval -3.61 to 0.49

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

This change from baseline reflects the Week 26 sitting diastolic blood pressure (DBP) minus the Week 0 sitting DBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach)	-2.38 mmHg Interval -3.51 to -1.25	-2.36 mmHg Interval -3.5 to -1.22	-0.96 mmHg Interval -2.16 to 0.24

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

This change from baseline reflects the Week 26 sitting diastolic blood pressure (DBP) minus the Week 0 sitting DBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach) (China Subpopulation)	-2.82 mmHg Interval -4.11 to -1.54	-2.77 mmHg Interval -4.09 to -1.45	-1.82 mmHg Interval -3.21 to -0.43

SECONDARY outcome

Timeframe: Week 26

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants With HbA1c of <6.5% (48 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach)	14.7 Percentage of participants	15.4 Percentage of participants	2.4 Percentage of participants

SECONDARY outcome

Timeframe: Week 26

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one assessment of the respective endpoint at baseline or post baseline up to Week 26.

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants With HbA1c of <6.5% (48 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) (China Subpopulation)	14.7 Percentage of participants	17.0 Percentage of participants	3.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 26

Population: The analysis population included all randomized participants who received at least one dose of investigational product.

Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants Requiring Glycemic Rescue Therapy Through Week 26.	1.2 Percentage of Participants	0.6 Percentage of Participants	9.6 Percentage of Participants

SECONDARY outcome

Timeframe: Week 26

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product.

Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=135 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Percentage of Participants Requiring Glycemic Rescue Therapy Through Week 26 (China Subpopulation)	0.0 Percentage of Participants	0.7 Percentage of Participants	9.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 183 days

Population: The analysis population included all randomized participants who received at least one dose of investigational product who received glycemic rescue through Week 26.

Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment.

Outcome measures

Measure	Ertugliflozin 5 mg n=2 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=1 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=16 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Time to Glycemic Rescue Therapy	NA Days Interval 41.0 to 85.0 The median is not estimable due to the low number of participants rescued.	NA Days Interval 149.0 to 149.0 The median is not estimable due to the low number of participants rescued.	NA Days Interval 22.0 to 183.0 The median is not estimable due to the low number of participants rescued.

SECONDARY outcome

Timeframe: Up to 149 days

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who received glycemic rescue through Week 26. No participants in the Ertugliflozin 5 mg group were rescued.

Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment.

Outcome measures

Measure	Ertugliflozin 5 mg Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=1 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=13 Participants Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Time to Glycemic Rescue Therapy (China Subpopulation)	—	NA Days Interval 149.0 to 149.0 The median is not estimable due to the low number of participants rescued.	NA Days Interval 22.0 to 145.0 The median is not estimable due to the low number of participants rescued.

SECONDARY outcome

Timeframe: Week 6: Pre-Dose

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach	9.17 ng/mL Standard Deviation 18.39	24.59 ng/mL Standard Deviation 43.84	—

SECONDARY outcome

Timeframe: Week 12: Pre-Dose

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach	8.18 ng/mL Standard Deviation 15.25	27.11 ng/mL Standard Deviation 66.02	—

SECONDARY outcome

Timeframe: Week 12: 60 min. Post-Dose

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach	91.49 ng/mL Standard Deviation 50.61	277.60 ng/mL Standard Deviation 130.66	—

SECONDARY outcome

Timeframe: Week 18: Pre-Dose

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach	6.59 ng/mL Standard Deviation 12.53	17.54 ng/mL Standard Deviation 24.62	—

SECONDARY outcome

Timeframe: Week 18: 60 min. Post-Dose

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach	91.40 ng/mL Standard Deviation 44.77	274.23 ng/mL Standard Deviation 146.14	—

SECONDARY outcome

Timeframe: Week 26: Pre-Dose

Population: The analysis population included all randomized participants who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=170 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach	7.34 ng/mL Standard Deviation 14.18	26.66 ng/mL Standard Deviation 62.17	—

SECONDARY outcome

Timeframe: Week 6: Pre-Dose

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach (China Subpopulation)	7.88 ng/mL Standard Deviation 14.88	22.29 ng/mL Standard Deviation 42.81	—

SECONDARY outcome

Timeframe: Week 12: Pre-Dose

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=136 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=135 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach (China Subpopulation)	7.40 ng/mL Standard Deviation 12.21	23.84 ng/mL Standard Deviation 52.64	—

SECONDARY outcome

Timeframe: Week 12: 60 min. Post-Dose

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=131 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=125 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach (China Subpopulation)	97.36 ng/mL Standard Deviation 48.98	294.49 ng/mL Standard Deviation 124.73	—

SECONDARY outcome

Timeframe: Week 18: Pre-Dose

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=127 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=125 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach (China Subpopulation)	6.30 ng/mL Standard Deviation 11.50	17.07 ng/mL Standard Deviation 27.06	—

SECONDARY outcome

Timeframe: Week 18: 60 min. Post-Dose

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=127 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=125 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach (China Subpopulation)	94.82 ng/mL Standard Deviation 41.40	285.28 ng/mL Standard Deviation 141.59	—

SECONDARY outcome

Timeframe: Week 26: Pre-Dose

Population: The analysis population included all randomized participants in China who received at least one dose of investigational product and who had at least one plasma concentration value above the lower limit of quantification. No ertugliflozin plasma concentrations were determined for participants receiving placebo.

No ertugliflozin plasma concentrations were determined for participants receiving placebo. Lower limit of quantification for ertugliflozin was 0.500 ng/mL.

Outcome measures

Measure	Ertugliflozin 5 mg n=127 Participants Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=118 Participants Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin Plasma Concentrations Summary Statistics Over Time: Including Rescue Approach (China Subpopulation)	7.26 ng/mL Standard Deviation 14.09	24.91 ng/mL Standard Deviation 57.95	—

Adverse Events

Ertugliflozin 5 mg

Serious events: 9 serious events

Other events: 22 other events

Deaths: 0 deaths

Ertugliflozin 15 mg

Serious events: 10 serious events

Other events: 31 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ertugliflozin 5 mg n=170 participants at risk Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 participants at risk Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 participants at risk Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Blood and lymphatic system disorders Iron deficiency anaemia	0.59% 1/170 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Cardiac disorders Microvascular coronary artery disease	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Ear and labyrinth disorders Vertigo positional	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Eye disorders Cataract	0.59% 1/170 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Eye disorders Dacryostenosis acquired	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Gastrointestinal disorders Intestinal polyp	0.59% 1/170 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Hepatobiliary disorders Cholecystitis chronic	0.59% 1/170 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Infections and infestations Pneumonia	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Injury, poisoning and procedural complications Craniocerebral injury	0.59% 1/170 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Injury, poisoning and procedural complications Limb injury	0.59% 1/170 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Injury, poisoning and procedural complications Patella fracture	0.59% 1/170 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Investigations Blood glucose increased	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.60% 1/167 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.59% 1/170 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.59% 1/170 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clear cell renal cell carcinoma	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Nervous system disorders Cerebellar infarction	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Nervous system disorders Cubital tunnel syndrome	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/169 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.60% 1/167 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.
Renal and urinary disorders Hydronephrosis	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/170 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.59% 1/169 • Number of events 1 • Up to 28 weeks The analysis population included all randomized and treated participants.	0.00% 0/167 • Up to 28 weeks The analysis population included all randomized and treated participants.

Other adverse events

Measure	Ertugliflozin 5 mg n=170 participants at risk Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Ertugliflozin 15 mg n=169 participants at risk Ertugliflozin 15 mg administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.	Placebo n=167 participants at risk Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Infections and infestations Nasopharyngitis	5.3% 9/170 • Number of events 13 • Up to 28 weeks The analysis population included all randomized and treated participants.	5.3% 9/169 • Number of events 11 • Up to 28 weeks The analysis population included all randomized and treated participants.	6.6% 11/167 • Number of events 13 • Up to 28 weeks The analysis population included all randomized and treated participants.
Infections and infestations Upper respiratory tract infection	2.4% 4/170 • Number of events 4 • Up to 28 weeks The analysis population included all randomized and treated participants.	5.3% 9/169 • Number of events 9 • Up to 28 weeks The analysis population included all randomized and treated participants.	8.4% 14/167 • Number of events 16 • Up to 28 weeks The analysis population included all randomized and treated participants.
Metabolism and nutrition disorders Hyperuricaemia	2.9% 5/170 • Number of events 5 • Up to 28 weeks The analysis population included all randomized and treated participants.	5.3% 9/169 • Number of events 9 • Up to 28 weeks The analysis population included all randomized and treated participants.	12.0% 20/167 • Number of events 21 • Up to 28 weeks The analysis population included all randomized and treated participants.
Metabolism and nutrition disorders Hypoglycaemia	3.5% 6/170 • Number of events 10 • Up to 28 weeks The analysis population included all randomized and treated participants.	5.3% 9/169 • Number of events 10 • Up to 28 weeks The analysis population included all randomized and treated participants.	1.2% 2/167 • Number of events 2 • Up to 28 weeks The analysis population included all randomized and treated participants.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee Investigator will provide manuscripts, abstracts, or the full text of any other intended disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to the sponsor at least 30 days before they are submitted for publication or otherwise disclosed. If any patent action is required to protect intellectual property rights, Investigator agrees to delay the disclosure for a period not to exceed an additional 60 days.
• Publication restrictions are in place

Restriction type: OTHER