Trial Outcomes & Findings for Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006; VERTIS SITA2) (NCT NCT02036515)

Results Overview

A1C is measured as percent. Thus this change from baseline reflects the Week 26 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

464 participants

Primary outcome timeframe

Baseline and Week 26

Results posted on

2018-09-13

Participant Flow

Two participants were randomized to Ertugliflozin 15 mg, but did not receive any treatment.

Participant milestones

Participant milestones
Measure	Ertugliflozin 5 mg Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Overall Study STARTED	156	155	153
Overall Study Treated	156	153	153
Overall Study COMPLETED	151	143	139
Overall Study NOT COMPLETED	5	12	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Ertugliflozin 5 mg Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Overall Study Adverse Event	1	1	2
Overall Study Lost to Follow-up	0	2	0
Overall Study Non-compliance with study drug	0	0	2
Overall Study Screen failure	0	2	0
Overall Study Withdrawal by Subject	4	7	9
Overall Study Hyperglycemia	0	0	1

Baseline Characteristics

Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006; VERTIS SITA2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks	Total n=462 Participants Total of all reporting groups
Age, Continuous	59.2 Years STANDARD_DEVIATION 9.3 • n=5 Participants	59.7 Years STANDARD_DEVIATION 8.6 • n=7 Participants	58.3 Years STANDARD_DEVIATION 9.2 • n=5 Participants	59.1 Years STANDARD_DEVIATION 9.0 • n=4 Participants
Sex: Female, Male Female	75 Participants n=5 Participants	71 Participants n=7 Participants	53 Participants n=5 Participants	199 Participants n=4 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	82 Participants n=7 Participants	100 Participants n=5 Participants	263 Participants n=4 Participants
Hemoglobin A1c (A1C)	8.05 Percent STANDARD_DEVIATION 0.86 • n=5 Participants	8.00 Percent STANDARD_DEVIATION 0.83 • n=7 Participants	8.03 Percent STANDARD_DEVIATION 0.93 • n=5 Participants	8.03 Percent STANDARD_DEVIATION 0.88 • n=4 Participants
Fasting plasma glucose	167.7 mg/dL STANDARD_DEVIATION 37.7 • n=5 Participants	171.7 mg/dL STANDARD_DEVIATION 39.1 • n=7 Participants	169.6 mg/dL STANDARD_DEVIATION 37.8 • n=5 Participants	169.7 mg/dL STANDARD_DEVIATION 38.2 • n=4 Participants
Body weight	87.6 Kilograms STANDARD_DEVIATION 18.6 • n=5 Participants	86.6 Kilograms STANDARD_DEVIATION 19.5 • n=7 Participants	86.4 Kilograms STANDARD_DEVIATION 20.8 • n=5 Participants	86.9 Kilograms STANDARD_DEVIATION 19.6 • n=4 Participants
Estimated glomerular filtration rate (eGFR)	87.0 mL/min/1.73m^2 STANDARD_DEVIATION 17.5 • n=5 Participants	86.9 mL/min/1.73m^2 STANDARD_DEVIATION 15.6 • n=7 Participants	89.9 mL/min/1.73m^2 STANDARD_DEVIATION 17.5 • n=5 Participants	87.9 mL/min/1.73m^2 STANDARD_DEVIATION 16.9 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one A1C measurement (baseline or post-baseline).

A1C is measured as percent. Thus this change from baseline reflects the Week 26 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in Hemoglobin A1C at Week 26	-0.78 Percent Interval -0.91 to -0.65	-0.86 Percent Interval -0.99 to -0.72	-0.09 Percent Interval -0.23 to -0.04

PRIMARY outcome

Timeframe: Up to Week 54

Population: Analysis population consisted of all randomized participants who took at least one dose of study medication.

An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Percentage of Participants Experiencing An Adverse Event (AE)	57.7 Percentage of participants	60.1 Percentage of participants	63.4 Percentage of participants

PRIMARY outcome

Timeframe: Up to Week 52

Population: Analysis population consisted of all randomized participants who took at least one dose of study medication.

An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Percentage of Participants Discontinuing Study Treatment Due to an AE	4.5 Percentage of participants	3.9 Percentage of participants	3.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one FPG measurement (baseline or post-baseline).

The change from baseline is the Week 26 FPG minus the Week 0 FPG. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	-26.91 mg/dL 95% Confidence Interval -32.58 • Interval -32.58 to -21.24	-33.04 mg/dL Interval -38.71 to -27.36	-1.76 mg/dL Interval -7.7 to 4.18

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one body weight measurement (baseline or post-baseline).

The change from baseline is the Week 26 body weight minus the Week 0 body weight. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in Body Weight at Week 26	-3.35 kg Interval -3.78 to -2.91	-3.04 kg Interval -3.48 to -2.6	-1.32 kg Interval -1.77 to -0.87

SECONDARY outcome

Timeframe: Week 26

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one A1C measurement (baseline or post-baseline).

A1C is measured as percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 26	32.1 Percentage of participants	39.9 Percentage of participants	17.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one systolic blood pressure measurement (baseline or post-baseline).

The change from baseline is the Week 26 systolic blood pressure minus the Week 0 systolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 Baseline	130.87 mmHg Standard Error 0.62 • Interval -5.52 to -2.09	130.87 mmHg Standard Error 0.62 • Interval -6.55 to -3.09	130.87 mmHg Standard Error 0.62 • Interval -2.7 to 0.94
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 Change from baseline	-3.81 mmHg Standard Error 0.87	-4.82 mmHg Standard Error 0.88	-0.88 mmHg Standard Error 0.93

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one A1C measurement (baseline or post-baseline).

A1C is measured as percent. Thus this change from baseline reflects the Week 52 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in Hemoglobin A1C at Week 52	-0.75 Percent Interval -0.9 to -0.59	-0.81 Percent Interval -0.97 to -0.66	0.02 Percent Interval -0.15 to 0.19

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one FPG measurement (baseline or post-baseline).

The change from baseline is the Week 52 FPG minus the Week 0 FPG. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in FPG at Week 52	-25.57 mg/dL Interval -30.91 to -20.23	-26.38 mg/dL Interval -31.8 to -20.97	3.19 mg/dL Interval -3.08 to 9.47

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one body weight measurement (baseline or post-baseline).

The change from baseline is the Week 52 body weight minus the Week 0 body weight. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in Body Weight at Week 52	-3.46 kg Interval -4.07 to -2.85	-2.83 kg Interval -3.45 to -2.21	-0.95 kg Interval -1.65 to -0.26

SECONDARY outcome

Timeframe: Week 52

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one A1C measurement (baseline or post-baseline).

A1C is measured as percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 52	33.3 Percentage of participants	32.7 Percentage of participants	13.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one systolic blood pressure measurement (baseline or post-baseline).

The change from baseline is the Week 52 systolic blood pressure minus the Week 0 systolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in Sitting Systolic Blood Pressure at Week 52 Baseline	130.92 mmHg Standard Error 0.62 • Interval -6.03 to -2.29	130.92 mmHg Standard Error 0.62 • Interval -5.98 to -2.2	130.92 mmHg Standard Error 0.62 • Interval -1.41 to 3.06
Change From Baseline in Sitting Systolic Blood Pressure at Week 52 Change from baseline	-4.16 mmHg Standard Error 0.95	-4.09 mmHg Standard Error 0.96	0.83 mmHg Standard Error 1.14

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one diastolic blood pressure measurement (baseline or post-baseline).

The change from baseline is the Week 26 diastolic blood pressure minus the Week 0 diastolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 Baseline	78.42 mmHg Standard Error 0.36 • Interval -2.88 to -0.48	78.42 mmHg Standard Error 0.36 • Interval -3.02 to -0.6	78.42 mmHg Standard Error 0.36 • Interval -1.71 to 0.84
Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 Change from baseline	-1.68 mmHg Standard Error 0.61	-1.81 mmHg Standard Error 0.62	-0.43 mmHg Standard Error 0.65

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one diastolic blood pressure measurement (baseline or post-baseline).

The change from baseline is the Week 52 diastolic blood pressure minus the Week 0 diastolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 Baseline	78.44 mmHg Standard Error 0.36 • Interval -2.72 to -0.32	78.44 mmHg Standard Error 0.36 • Interval -2.59 to -0.17	78.44 mmHg Standard Error 0.36 • Interval -1.97 to 0.91
Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 Change from baseline	-1.52 mmHg Standard Error 0.61	-1.38 mmHg Standard Error 0.62	-0.53 mmHg Standard Error 0.73

SECONDARY outcome

Timeframe: Week 26

Population: Analysis population included all randomized participants who took at least one dose of trial treatment.

Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant).

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Percentage of Participants Receiving Glycemic Rescue Medication by Week 26	1.3 Percentage of participants	2.0 Percentage of participants	16.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: Analysis population included all randomized participants who took at least one dose of trial treatment.

Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant).

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Percentage of Participants Receiving Glycemic Rescue Medication by Week 52	12.8 Percentage of participants	13.7 Percentage of participants	41.8 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 26 (plus 30 days for 1 placebo participant)

Population: Analysis population included all randomized participants who took at least one dose of trial treatment

Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant). Data presented are the minimum and maximum times to the initiation of rescue therapy in days. Below data include data from 1 participant in the Placebo arm who continued Phase A treatment for an additional 30 days.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Time to Initiation of Glycemic Rescue by Week 26 Minimum time to initiation of glycemic rescue	135 Days	43 Days	26 Days
Time to Initiation of Glycemic Rescue by Week 26 Maximum time to initiation of glycemic rescue	141 Days	147 Days	212 Days

SECONDARY outcome

Timeframe: Up to week 52

Population: Analysis population included all randomized participants who took at least one dose of trial treatment.

Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant). Data presented are the minimum and maximum times to the initiation of rescue therapy in days.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=156 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=153 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Time to Initiation of Glycemic Rescue by Week 52 Minimum time to initiation of glycemic rescue	135 Days	43 Days	26 Days
Time to Initiation of Glycemic Rescue by Week 52 Maximum time to initiation of glycemic rescue	295 Days	299 Days	327 Days

SECONDARY outcome

Timeframe: Baseline

Population: Analysis population included all randomized participants who took at least one dose of study medication and had HOMA-%β measurement at baseline.

HOMA-%β is a well-accepted means of assessing fasting β-cell function, and is calculated using measured C-peptide and glucose levels and is measured as a percentage of a normal reference population. HOMA-%β = \[20 x fasting insulin (μU/mL)\] / \[fasting plasma glucose (mmol/L) - 3.5\]

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=140 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=131 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=127 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Baseline Homeostasis Model Assessment of β-cell Function (HOMA-%β) Value	47.99 Percentage Standard Deviation 23.890 • Interval 8.87 to 17.68	48.54 Percentage Standard Deviation 34.782 • Interval 7.94 to 16.93	48.04 Percentage Standard Deviation 30.733 • Interval -4.08 to 5.12

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one HOMA-%β measurement (baseline or post-baseline).

HOMA-%β is a well-accepted means of assessing fasting β-cell function, and is calculated using measured C-peptide and glucose levels and is measured as a percentage of a normal reference population. HOMA-%β = \[20 x fasting insulin (μU/mL)\] / \[fasting plasma glucose (mmol/L) - 3.5\]. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=153 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=151 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=147 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in HOMA-%β at Week 26	13.28 Percentage Interval 8.87 to 17.68	12.43 Percentage Interval 7.94 to 16.93	0.52 Percentage Interval -4.08 to 5.12

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one HOMA-%β measurement (baseline or post-baseline).

HOMA-%β is a well-accepted means of assessing fasting β-cell function, and is calculated using measured C-peptide and glucose levels and is measured as a percentage of a normal reference population. HOMA-%β = \[20 x fasting insulin (μU/mL)\] / \[fasting plasma glucose (mmol/L) - 3.5\]. Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=155 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=152 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=152 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in HOMA-%β at Week 52	10.85 Percentage Interval 6.29 to 15.41	10.93 Percentage Interval 6.24 to 15.61	-1.93 Percentage Interval -6.88 to 3.02

SECONDARY outcome

Timeframe: Baseline

Population: Analysis population included all randomized participants who took at least one dose of study medication and had a baseline EQ-5D-3L measurement.

The EQ-5D-3L is a health profile questionnaire that assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 1-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also includes an EQ visual analogue score (VAS) that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best).

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=150 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=150 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=152 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Baseline EQ-5D 3-level Version (EQ-5D-3L) Questionnaire Score	0.88 Score on a scale Standard Deviation 0.166 • Interval -0.02 to 0.03	0.89 Score on a scale Standard Deviation 0.182 • Interval 0.0 to 0.04	0.90 Score on a scale Standard Deviation 0.144 • Interval -0.01 to 0.04

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one EQ-5D-3L measurement (baseline or post-baseline).

The EQ-5D-3L is a health profile questionnaire that assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 3-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also includes an EQ VAS that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best). Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=155 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=151 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in EQ-5D-3L Questionnaire Score at Week 26	0.00 Score on a scale Interval -0.02 to 0.03	0.02 Score on a scale Interval 0.0 to 0.04	0.01 Score on a scale Interval -0.01 to 0.04

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Analysis population included all randomized participants who took at least one dose of study medication and had at least one EQ-5D-3L measurement (baseline or post-baseline).

The EQ-5D-3L is a health profile questionnaire that assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 3-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also includes an EQ VAS that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best). Data presented exclude data following the initiation of rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=155 Participants Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg n=151 Participants Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo n=153 Participants Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Change From Baseline in EQ-5D-3L Score at Week 52	0.03 Score on a scale Interval 0.0 to 0.05	-0.00 Score on a scale Interval -0.03 to 0.03	0.02 Score on a scale Interval -0.01 to 0.06

Adverse Events

Ertugliflozin 5 mg (Phase A+B)

Serious events: 13 serious events

Other events: 24 other events

Deaths: 0 deaths

Ertugliflozin 15 mg (Phase A+B)

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo (Phase A+B)

Serious events: 8 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ertugliflozin 5 mg (Phase A+B) n=156 participants at risk Ertugliflozin, 5 mg, oral, once daily for 52 weeks	Ertugliflozin 15 mg (Phase A+B) n=153 participants at risk Ertugliflozin, 15 mg, oral, once daily for 52 weeks	Placebo (Phase A+B) n=153 participants at risk Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Infections and infestations Nasopharyngitis	5.1% 8/156 • Number of events 8 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables	3.9% 6/153 • Number of events 6 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables	3.3% 5/153 • Number of events 6 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables
Infections and infestations Urinary tract infection	1.3% 2/156 • Number of events 2 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables	3.3% 5/153 • Number of events 5 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables	5.2% 8/153 • Number of events 9 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables
Metabolism and nutrition disorders Hypoglycaemia	4.5% 7/156 • Number of events 16 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables	3.3% 5/153 • Number of events 11 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables	7.2% 11/153 • Number of events 18 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables
Musculoskeletal and connective tissue disorders Back pain	5.1% 8/156 • Number of events 8 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables	2.0% 3/153 • Number of events 3 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables	3.9% 6/153 • Number of events 6 • Up to 54 weeks Data presented below includes data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). Two participants randomized to ertugliflozin 15 mg didn't receive any study medication \& aren't included in the below tables

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER