Trial Outcomes & Findings for Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus on Background of Metformin (NCT NCT02926950)

NCT ID: NCT02926950

Last Updated: 2021-05-11

Results Overview

An analysis of covariance (ANCOVA) model was used for the analysis.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 518 participants
• Primary outcome timeframe: Baseline and Week 26
• Results posted on: 2021-05-11

Participant Flow

Participants took part in the study at 87 investigative sites in Canada, Hungary, Slovakia and the United States from 11 November 2016 to 22 March 2019.

Participants with a diagnosis of type 2 Diabetes Mellitus were enrolled in 1 of 2 treatment groups, Sotagliflozin 400 milligrams (mg) once daily (QD) + Metformin and Placebo + Metformin. Participants were randomly assigned to the ratio of 1:1 to these reporting groups.

Participant milestones

Measure	Placebo + Metformin Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Overall Study STARTED	259	259
Overall Study COMPLETED	210	211
Overall Study NOT COMPLETED	49	48

Reasons for withdrawal

Measure	Placebo + Metformin Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Overall Study Adverse Event	4	6
Overall Study At the participant's own request	21	25
Overall Study Reason not Specified	17	9
Overall Study Lost to Follow-up	7	8

Baseline Characteristics

Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus on Background of Metformin

Baseline characteristics by cohort

Measure	Placebo + Metformin n=259 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Total n=518 Participants Total of all reporting groups
Age, Continuous	59.9 years STANDARD_DEVIATION 9.4 • n=93 Participants	60.0 years STANDARD_DEVIATION 10.1 • n=4 Participants	59.9 years STANDARD_DEVIATION 9.8 • n=27 Participants
Sex: Female, Male Female	113 Participants n=93 Participants	117 Participants n=4 Participants	230 Participants n=27 Participants
Sex: Female, Male Male	146 Participants n=93 Participants	142 Participants n=4 Participants	288 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	106 Participants n=93 Participants	117 Participants n=4 Participants	223 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	153 Participants n=93 Participants	140 Participants n=4 Participants	293 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) Asian	19 Participants n=93 Participants	6 Participants n=4 Participants	25 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Black or African American	40 Participants n=93 Participants	28 Participants n=4 Participants	68 Participants n=27 Participants
Race (NIH/OMB) White	197 Participants n=93 Participants	223 Participants n=4 Participants	420 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Hemoglobin A1c (HbA1c)	8.19 percentage of HbA1c STANDARD_DEVIATION 0.82 • n=93 Participants	8.20 percentage of HbA1c STANDARD_DEVIATION 0.78 • n=4 Participants	8.20 percentage of HbA1c STANDARD_DEVIATION 0.80 • n=27 Participants
Systolic Blood Pressure (SBP)	133.80 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.95 • n=93 Participants	134.06 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.95 • n=4 Participants	133.93 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.93 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: Intent-to-treat (ITT) population included all randomized participants. Missing data was imputed using the retrieved dropouts and washout imputation method.

An analysis of covariance (ANCOVA) model was used for the analysis.

Outcome measures

Measure	Placebo + Metformin n=259 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26	-0.29 percentage of HbA1c Standard Error 0.079	-0.77 percentage of HbA1c Standard Error 0.077

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: ITT population included all randomized participants. Missing data are imputed using control-based copy reference multiple imputation method.

An ANCOVA model was used for the analysis.

Outcome measures

Measure	Placebo + Metformin n=259 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26	-0.930 millimole per liter (mmol/L) Standard Error 0.2353	-2.502 millimole per liter (mmol/L) Standard Error 0.2292

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: ITT population included all randomized participants. Missing data was imputed using the retrieved dropouts and washout imputation method.

An ANCOVA model was used for the analysis.

Outcome measures

Measure	Placebo + Metformin n=259 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	-0.550 mmol/L Standard Error 0.1864	-1.310 mmol/L Standard Error 0.2089

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: ITT population included all randomized participants. Missing data was imputed using the retrieved dropouts and washout imputation method.

An ANCOVA model was used for the analysis.

Outcome measures

Measure	Placebo + Metformin n=259 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Change From Baseline in Body Weight at Week 26	-0.69 kilogram (kg) Standard Error 0.310	-2.56 kilogram (kg) Standard Error 0.331

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Analysis was performed on ITT population in participant with baseline SBP ≥130 mmHg. Missing data was imputed using control-based copy reference multiple imputation method.

An ANCOVA model was used for the analysis.

Outcome measures

Measure	Placebo + Metformin n=129 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=137 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 mmHg	-6.92 millimeter of mercury (mmHg) Standard Error 1.233	-10.21 millimeter of mercury (mmHg) Standard Error 1.270

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included all randomized participants. Missing data was imputed using control-based copy reference multiple imputation method.

An ANCOVA model was used for the analysis.

Outcome measures

Measure	Placebo + Metformin n=259 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Change From Baseline in SBP at Week 12 for All Participants	-1.87 mmHg Standard Error 0.949	-5.41 mmHg Standard Error 0.950

SECONDARY outcome

Timeframe: Week 26

Population: ITT population included all randomized participants.

Outcome measures

Measure	Placebo + Metformin n=259 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Percentage of Participants With HbA1c <6.5% at Week 26	5.4 percentage of participants	10.8 percentage of participants

SECONDARY outcome

Timeframe: Week 26

Population: ITT population included all randomized participants.

Outcome measures

Measure	Placebo + Metformin n=259 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Percentage of Participants With HbA1c <7.0% at Week 26	15.8 percentage of participants	29.7 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 79 weeks in the treatment period

Population: Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product.

Percentage of participants with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia [typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤70 mg/dL (3.9 mmol/L)]; Severe [an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions] or documented symptomatic hypoglycemia [typical symptoms of hypoglycemia and plasma glucose ≤70 mg/dL]. Participants may be reported in more than one category.

Outcome measures

Measure	Placebo + Metformin n=259 Participants Following a 2-week run-in period, matching placebo was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 Participants Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, QD, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Percentage of Participants With Hypoglycemic Events Any hypoglycemia	11.6 percentage of participants	6.6 percentage of participants
Percentage of Participants With Hypoglycemic Events Documented symptomatic hypoglycemia	6.2 percentage of participants	3.1 percentage of participants
Percentage of Participants With Hypoglycemic Events Severe or documented symptomatic hypoglycemia	6.2 percentage of participants	3.1 percentage of participants

Adverse Events

Placebo + Metformin

Serious events: 23 serious events

Other events: 109 other events

Deaths: 1 deaths

Sotagliflozin 400 mg + Metformin

Serious events: 19 serious events

Other events: 85 other events

Deaths: 3 deaths

Serious adverse events

Measure	Placebo + Metformin n=259 participants at risk Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 participants at risk Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Biliary neoplasm	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal papillary mucinous neoplasm	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive breast carcinoma	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal oncocytoma	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland cancer recurrent	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
General disorders Chest discomfort	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
General disorders Non-cardiac chest pain	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.77% 2/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
General disorders Pyrexia	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Reproductive system and breast disorders Cervical polyp	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Reproductive system and breast disorders Colpocele	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Injury, poisoning and procedural complications Acetabulum fracture	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Injury, poisoning and procedural complications Road traffic accident	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Investigations Alanine aminotransferase increased	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Investigations Blood bilirubin increased	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Cardiac disorders Acute myocardial infarction	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Cardiac disorders Angina pectoris	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.77% 2/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Cardiac disorders Atrial fibrillation	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Cardiac disorders Cardiopulmonary failure	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Cardiac disorders Coronary artery disease	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Cardiac disorders Myocardial infarction	0.77% 2/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Cardiac disorders Sinus tachycardia	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Carotid artery stenosis	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Cerebellar stroke	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Cerebral artery thrombosis	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Cerebrovascular accident	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Haemorrhagic cerebral infarction	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Intracranial venous sinus thrombosis	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Metabolic encephalopathy	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Subarachnoid haemorrhage	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Syncope	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Gastrointestinal disorders Pancreatitis acute	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Hepatobiliary disorders Cholecystitis acute	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Renal and urinary disorders Acute kidney injury	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Renal and urinary disorders Calculus urethral	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Renal and urinary disorders Renal cyst	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Renal and urinary disorders Renal failure	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Renal and urinary disorders Ureterolithiasis	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Skin and subcutaneous tissue disorders Neurodermatitis	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Musculoskeletal and connective tissue disorders Back pain	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.77% 2/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Metabolism and nutrition disorders Dehydration	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Abscess limb	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Cellulitis	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Device related infection	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Diverticulitis	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Influenza	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Osteomyelitis	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.77% 2/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Pneumonia	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	1.2% 3/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Septic shock	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Urinary tract infection	0.39% 1/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	0.00% 0/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.

Other adverse events

Measure	Placebo + Metformin n=259 participants at risk Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Sotagliflozin 400 mg + Metformin n=259 participants at risk Following a 2-week run-in period, Sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus Metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.
Vascular disorders Hypertension	5.0% 13/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	1.2% 3/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Nervous system disorders Headache	5.8% 15/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	2.3% 6/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Gastrointestinal disorders Diarrhoea	4.2% 11/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	8.5% 22/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Musculoskeletal and connective tissue disorders Back pain	7.3% 19/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	3.1% 8/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Metabolism and nutrition disorders Vitamin D deficiency	7.3% 19/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	5.4% 14/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Bronchitis	6.6% 17/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	1.9% 5/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Nasopharyngitis	6.6% 17/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	5.4% 14/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Upper respiratory tract infection	7.7% 20/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	7.7% 20/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Infections and infestations Urinary tract infection	5.8% 15/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.	6.2% 16/259 • First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Institution must provide any proposed publication or presentation to Sponsor for Sponsor's review, comment and approval at least thirty (30) days prior to the proposed submission for publication date or the proposed presentation date. Sponsor shall have the right to have deleted from the final version of the publication any confidential information, proprietary information, or patentable subject matter.
• Publication restrictions are in place

Restriction type: OTHER