SOTA-GLIM: Efficacy and Safety of Sotagliflozin Versus Glimepiride and Placebo in Participants With Type 2 Diabetes Mellitus That Are Taking Metformin Monotherapy

• Sponsor: Lexicon Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03332771
• Collaborator: Sanofi (Industry)
• Enrollment: 954
• Locations: 142
• Arms: 4
• Actual Duration (Months): 21.2
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate the non-inferiority of Sotagliflozin 400 milligrams (mg) compared to Glimepiride on hemoglobin A1c (HbA1c) reduction at Week 52 in participants with Type 2 Diabetes (T2D) who have inadequate glycemic control with metformin.

Secondary Objectives:

To demonstrate the superiority of Sotagliflozin 400 mg compared to Glimepiride on change in body weight, systolic blood pressure (SBP) in participants with baseline SBP ≥130 millimeter of mercury (mmHg), SBP in all participants, and proportion of participants with at least 1 documented symptomatic hypoglycemic event (≤70 milligrams per deciliter [mg/dL]).

• To demonstrate the superiority of Sotagliflozin 400 mg compared to placebo on change in HbA1c, body weight, SBP in participants with baseline SBP ≥130 mmHg, SBP in all participants.

• To demonstrate the superiority of Sotagliflozin 200 mg compared to placebo on change in HbA1c.

• To demonstrate the non-inferiority of Sotagliflozin 400 mg compared to Glimepiride on change in HbA1c.

• To demonstrate the superiority of Sotagliflozin 400 mg compared to Glimepiride on change in HbA1c.

• To evaluate the safety and tolerability of Sotagliflozin compared to Glimepiride and placebo.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Sotagliflozin (SAR439954); Drug: Glimepiride; Drug: Metformin; Drug: Placebo; Drug: Placebo	Phase 3

Detailed Description

Up to 58 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks, a 2-week single-blind placebo Run-in phase, a 52-week double-blind Treatment Period, and a 2-week post-treatment Follow-up period to collect safety information.

Study Design

• Study Type: Interventional
• Actual Enrollment: 954 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 52-week Randomized, Double-blind, Double-dummy, Active and Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Compared to Glimepiride or Placebo Added to Metformin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control With Metformin Monotherapy
• Actual Study Start Date: Dec 1, 2017
• Actual Primary Completion Date: Aug 6, 2019
• Actual Study Completion Date: Sep 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sotagliflozin 400 mg Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: tablet Route of administration: oral; Drug: Metformin; Pharmaceutical form: tablet Route of administration: oral; Drug: Placebo; Pharmaceutical form: capsule Route of administration: oral
Experimental: Sotagliflozin 200 mg Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: tablet Route of administration: oral; Drug: Metformin; Pharmaceutical form: tablet Route of administration: oral; Drug: Placebo; Pharmaceutical form: tablet Route of administration: oral; Drug: Placebo; Pharmaceutical form: capsule Route of administration: oral
Active Comparator: Glimepiride Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Drug: Glimepiride; Pharmaceutical form: capsule Route of administration: oral; Drug: Metformin; Pharmaceutical form: tablet Route of administration: oral; Drug: Placebo; Pharmaceutical form: tablet Route of administration: oral
Placebo Comparator: Placebo Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Drug: Metformin; Pharmaceutical form: tablet Route of administration: oral; Drug: Placebo; Pharmaceutical form: tablet Route of administration: oral; Drug: Placebo; Pharmaceutical form: capsule Route of administration: oral

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hemoglobin A1c at Week 52 [Baseline, Week 52]

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

Secondary Outcome Measures

1. Change From Baseline in Hemoglobin A1c at Week 26 [Baseline, Week 26]

   An ANCOVA model was used for the analysis.

2. Change From Baseline in Body Weight at Week 26 and 52 [Baseline, Week 26, Week 52]

   An ANCOVA model was used for the analysis.

3. Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP ≥130 mmHg at Week 12 [Baseline, Week 12]

   An ANCOVA model was used for the analysis.

4. Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12 [Baseline, Week 12]

   An ANCOVA model was used for the analysis.

5. Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event [Up to Week 52]

   Documented symptomatic hypoglycemia includes the 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).

6. Percentage of Participants With Adverse Events (AEs) [Up to Week 52]

   An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.

Other Outcome Measures

1. Percentage of Participants With Hypoglycemic Events [Up to Week 52]

   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].

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria :

• Participants with Type 2 Diabetes (T2D) treated with metformin at a stable dose ≥1500 milligrams per day (mg/day) or maximum tolerated dose (documented) for at least 12 weeks prior to Screening Visit; in case of documented lack of tolerance, metformin dose <1500 mg/day is acceptable, and the dose should be stable for at least 12 weeks prior to Screening Visit.

• Participants has given written informed consent to participate in the study in accordance with local regulations.

Exclusion criteria:

• Age <18 years at the Screening Visit or <legal age of majority, whichever is greater.

• Type 1 diabetes mellitus.

• HbA1c, HbA1c <7.0% or HbA1c >10% at Screening.

• Fasting Plasma Glucose (FPG) >15 millimoles per liter (mmol/L) (>270 milligram per deciliter [mg/dL]) measured by the central laboratory at Screening (Visit 1) and confirmed by a repeat test (>15 mmol/L [>270 mg/dL]) before randomization.

• Body mass index ≤20 or >45 kilogram per meter square (kg/m^2) at Screening.

• Pregnant (confirmed by pregnancy test at the Screening) or breast-feeding women.

• Women of childbearing potential (WOCBP) not willing to use highly effective method(s) of birth control during the study treatment period and the follow-up period, or who are unwilling or unable to be tested for pregnancy (see Appendix A) during the study.

• Previous use of any antidiabetic drug other than Metformin within 12 weeks preceding the Screening Visit.

• Use of a selective Sodium-glucose co-transporter-2 (SGLT2) inhibitor (e.g., Canagliflozin, Dapagliflozin, or Empagliflozin) within 3 months prior to the Screening visit.

• Use of systemic glucocorticoids (excluding topical, or ophthalmic application, intra-articular, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.

• Previous insulin use >1 month (at any time, except for treatment of gestational diabetes).

• History of prior gastric surgical procedure, including gastric banding, or inflammatory bowel disease within 3 years prior to the Screening Visit.

• Difficulty swallowing such that the participants cannot take the investigational medicinal product (IMP).

• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.

• Mean of 3 separate blood pressure measurements >180 millimeter of mercury (mmHg) (SBP) or >100 mmHg (DBP).

• History of hypertensive emergency within 12 weeks prior to Screening.

• Participants who have previously been randomized in any clinical trial of Sotagliflozin/LX4211.

• Participants with severe renal disease as defined by an estimated glomerular filtration rate (eGFR) of <30 milliliter per minute per meter square (mL/min/1.73 m^2) at Screening, based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation (or according to the renal function restrictions of metformin use defined in the local approved label).

• Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease that, according to Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.

• Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range (ULN).

• Total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome).

• Participants who have taken other investigational drugs within 12 weeks or 5 half-lives from Screening whichever is longer.

• Participants unwilling or unable to perform self-monitoring blood glucose (SMBG), complete the participant diary, or comply with study visits and other study procedures as required per protocol.

• Participants with contraindication to glimepiride as per local labelling.

• Participants with contraindication to metformin as per local labelling.

The above information is not intended to contain all considerations relevant to a Participants potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 8407040	Birmingham	Alabama	United States	35205
2	Investigational Site Number 8407048	Birmingham	Alabama	United States	35233-2110
3	Investigational Site Number 8407035	Little Rock	Arkansas	United States	72211
4	Investigational Site Number 8407051	Anaheim	California	United States	92801-2417
5	Investigational Site Number 8407065	Canoga Park	California	United States	91301
6	Investigational Site Number 8407078	Carmichael	California	United States	95608
7	Investigational Site Number 8407089	Downey	California	United States	90242
8	Investigational Site Number 8407011	Gold River	California	United States	95670
9	Investigational Site Number 8407044	Greenbrae	California	United States	94904
10	Investigational Site Number 8407006	Huntington Park	California	United States	90255-2911
11	Investigational Site Number 8407037	Lemon Grove	California	United States	91945
12	Investigational Site Number 8407100	Lomita	California	United States	90717
13	Investigational Site Number 8407033	Long Beach	California	United States	90806
14	Investigational Site Number 8407019	Los Angeles	California	United States	90057-3507
15	Investigational Site Number 8407098	Northridge	California	United States	91325-5409
16	Investigational Site Number 8407094	Norwalk	California	United States	90650
17	Investigational Site Number 8407106	Pomona	California	United States	91766
18	Investigational Site Number 8407096	Rancho Cucamonga	California	United States	91730
19	Investigational Site Number 8407036	Sacramento	California	United States	95821
20	Investigational Site Number 8407084	Tarzana	California	United States	91356-3551
21	Investigational Site Number 8407034	Upland	California	United States	91786-4070
22	Investigational Site Number 8407032	Van Nuys	California	United States	91405
23	Investigational Site Number 8407004	Walnut Creek	California	United States	94598
24	Investigational Site Number 8407117	Wildomar	California	United States	92595
25	Investigational Site Number 8407045	Colorado Springs	Colorado	United States	80920-8075
26	Investigational Site Number 8407074	Bradenton	Florida	United States	34201
27	Investigational Site Number 8407027	Clearwater	Florida	United States	33761
28	Investigational Site Number 8407103	Cooper City	Florida	United States	33024
29	Investigational Site Number 8407021	Coral Gables	Florida	United States	33134
30	Investigational Site Number 8407062	Lake Worth	Florida	United States	33467
31	Investigational Site Number 8407121	Ocoee	Florida	United States	34761
32	Investigational Site Number 8407024	Orlando	Florida	United States	32825-4454
33	Investigational Site Number 8407038	Palmetto Bay	Florida	United States	33157-5503
34	Investigational Site Number 8407093	Pembroke Pines	Florida	United States	33026-3924
35	Investigational Site Number 8407107	Spring Hill	Florida	United States	34609
36	Investigational Site Number 8407091	Tampa	Florida	United States	33619
37	Investigational Site Number 8407113	Tampa	Florida	United States	33634
38	Investigational Site Number 8407092	West Palm Beach	Florida	United States	33401
39	Investigational Site Number 8407115	Winter Haven	Florida	United States	33880
40	Investigational Site Number 8407017	Chicago	Illinois	United States	60607
41	Investigational Site Number 8407018	Elgin	Illinois	United States	60124
42	Investigational Site Number 8407046	Gurnee	Illinois	United States	60031
43	Investigational Site Number 8407119	Springfield	Illinois	United States	62711
44	Investigational Site Number 8407075	Waterloo	Iowa	United States	50702
45	Investigational Site Number 8407120	West Des Moines	Iowa	United States	50265
46	Investigational Site Number 8407095	Topeka	Kansas	United States	66606-2806
47	Investigational Site Number 8407083	Wichita	Kansas	United States	67205-1138
48	Investigational Site Number 8407043	Lexington	Kentucky	United States	40503-2517
49	Investigational Site Number 8407087	Lexington	Kentucky	United States	40503
50	Investigational Site Number 8407060	Lake Charles	Louisiana	United States	70601
51	Investigational Site Number 8407058	New Orleans	Louisiana	United States	70119
52	Investigational Site Number 8407009	New Orleans	Louisiana	United States	70124
53	Investigational Site Number 8407079	Zachary	Louisiana	United States	70791-4010
54	Investigational Site Number 8407085	Baltimore	Maryland	United States	21237
55	Investigational Site Number 8407001	Rockville	Maryland	United States	20852
56	Investigational Site Number 8407069	Troy	Michigan	United States	48098-6334
57	Investigational Site Number 8407110	Olive Branch	Mississippi	United States	38654
58	Investigational Site Number 8407054	Bridgeton	Missouri	United States	63044
59	Investigational Site Number 8407049	Norfolk	Nebraska	United States	68701
60	Investigational Site Number 8407039	Omaha	Nebraska	United States	68114
61	Investigational Site Number 8407061	Papillion	Nebraska	United States	68046-3136
62	Investigational Site Number 8407108	Las Vegas	Nevada	United States	89106-4132
63	Investigational Site Number 8407050	Albuquerque	New Mexico	United States	87106
64	Investigational Site Number 8407116	New York	New York	United States	10016-6402
65	Investigational Site Number 8407086	New York	New York	United States	10029
66	Investigational Site Number 8407122	New York	New York	United States	10036
67	Investigational Site Number 8407123	West Seneca	New York	United States	14224
68	Investigational Site Number 8407020	Greensboro	North Carolina	United States	27408
69	Investigational Site Number 8407114	Lenoir	North Carolina	United States	28645-8981
70	Investigational Site Number 8407015	Morehead City	North Carolina	United States	28557
71	Investigational Site Number 8407030	Salisbury	North Carolina	United States	28144-2742
72	Investigational Site Number 8407041	Wilmington	North Carolina	United States	28401-6638
73	Investigational Site Number 8407101	Winston-Salem	North Carolina	United States	27103
74	Investigational Site Number 8407099	Cincinnati	Ohio	United States	45245
75	Investigational Site Number 8407081	Lyndhurst	Ohio	United States	44124-2467
76	Investigational Site Number 8407057	Norman	Oklahoma	United States	73069
77	Investigational Site Number 8407073	Oklahoma City	Oklahoma	United States	73104-3252
78	Investigational Site Number 8407068	Eugene	Oregon	United States	97404
79	Investigational Site Number 8407104	Beaver	Pennsylvania	United States	15009-1957
80	Investigational Site Number 8407025	Hatboro	Pennsylvania	United States	19040-2045
81	Investigational Site Number 8407053	Lansdale	Pennsylvania	United States	19446-1002
82	Investigational Site Number 8407016	Charleston	South Carolina	United States	29407
83	Investigational Site Number 8407071	Greer	South Carolina	United States	29651-1817
84	Investigational Site Number 8407022	Mount Pleasant	South Carolina	United States	29464
85	Investigational Site Number 8407031	Mount Pleasant	South Carolina	United States	29464
86	Investigational Site Number 8407014	Jefferson City	Tennessee	United States	37760
87	Investigational Site Number 8407002	Knoxville	Tennessee	United States	37938
88	Investigational Site Number 8407056	Memphis	Tennessee	United States	38163
89	Investigational Site Number 8407026	Austin	Texas	United States	78735-8982
90	Investigational Site Number 8407029	Beaumont	Texas	United States	77702
91	Investigational Site Number 8407070	Carrollton	Texas	United States	75010
92	Investigational Site Number 8407102	Corpus Christi	Texas	United States	78414-4173
93	Investigational Site Number 8407023	Dallas	Texas	United States	75230
94	Investigational Site Number 8407111	Dallas	Texas	United States	75231
95	Investigational Site Number 8407013	Fort Worth	Texas	United States	76164
96	Investigational Site Number 8407080	Houston	Texas	United States	77040
97	Investigational Site Number 8407088	Houston	Texas	United States	77095-2856
98	Investigational Site Number 8407090	Katy	Texas	United States	77450
99	Investigational Site Number 8407042	Lampasas	Texas	United States	76550-1820
100	Investigational Site Number 8407067	Lufkin	Texas	United States	75904
101	Investigational Site Number 8407118	Lufkin	Texas	United States	75904
102	Investigational Site Number 8407059	McAllen	Texas	United States	78504
103	Investigational Site Number 8407012	Mesquite	Texas	United States	75149
104	Investigational Site Number 8407007	Plano	Texas	United States	75075
105	Investigational Site Number 8407005	San Antonio	Texas	United States	78218
106	Investigational Site Number 8407064	San Antonio	Texas	United States	78229-3818
107	Investigational Site Number 8407010	Schertz	Texas	United States	78154
108	Investigational Site Number 8407076	Splendora	Texas	United States	77372
109	Investigational Site Number 8407063	Clinton	Utah	United States	84015
110	Investigational Site Number 8407055	Holladay	Utah	United States	84117-7054
111	Investigational Site Number 8407097	Ogden	Utah	United States	84405
112	Investigational Site Number 8407072	Salt Lake City	Utah	United States	84102-1553
113	Investigational Site Number 8407124	Manassas	Virginia	United States	20110-4421
114	Investigational Site Number 8407105	Richmond	Virginia	United States	23249-0001
115	Investigational Site Number 8407028	Renton	Washington	United States	98055
116	Investigational Site Number 1007002	Gabrovo		Bulgaria	5300
117	Investigational Site Number 1007008	Plovdiv		Bulgaria	4000
118	Investigational Site Number 1007003	Plovdiv		Bulgaria	4002
119	Investigational Site Number 1007001	Ruse		Bulgaria	7003
120	Investigational Site Number 1007004	Smolyan		Bulgaria	4700
121	Investigational Site Number 1007009	Sofia		Bulgaria	1632
122	Investigational Site Number 1007005	Stara Zagora		Bulgaria	6000
123	Investigational Site Number 1007006	Stara Zagora		Bulgaria	6000
124	Investigational Site Number 1007007	Varna		Bulgaria	9000
125	Investigational Site Number 3487005	Balatonfured		Hungary	8230
126	Investigational Site Number 3487001	Budapest		Hungary	1033
127	Investigational Site Number 3487010	Budapest		Hungary	1134
128	Investigational Site Number 3487006	Debrecen		Hungary	4025
129	Investigational Site Number 3487008	Debrecen		Hungary	4032
130	Investigational Site Number 3487002	Kecskemet		Hungary	6000
131	Investigational Site Number 3487007	Nyiregyhaza		Hungary	4405
132	Investigational Site Number 3487004	Nyíregyháza		Hungary	4400
133	Investigational Site Number 7037004	Bardejov		Slovakia	085 01
134	Investigational Site Number 7037008	Bratislava		Slovakia	831 06
135	Investigational Site Number 7037007	Bratislava		Slovakia	85101
136	Investigational Site Number 7037005	Kosice		Slovakia	4014
137	Investigational Site Number 7037002	Levice		Slovakia	934 01
138	Investigational Site Number 7037010	Nitra		Slovakia	94901
139	Investigational Site Number 7037009	Roznava		Slovakia	048 01
140	Investigational Site Number 7037001	Sabinov		Slovakia	08301
141	Investigational Site Number 7037003	Trnava		Slovakia	91701
142	Investigational Site Number 7037006	Vrutky		Slovakia	038 61

Sponsors and Collaborators

• Lexicon Pharmaceuticals
• Sanofi

Investigators

• Study Director: Suman Wason, MD, Lexicon Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - Apr 11, 2018
• Statistical Analysis Plan - Apr 15, 2020

More Information

Publications

None provided.

• Responsible Party: Lexicon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03332771
• Other Study ID Numbers: EFC14838; 2016-001801-17; U1111-1190-7596
• First Posted: Nov 6, 2017
• Last Update Posted: May 11, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Glimepiride; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 138 investigative sites in United States, Bulgaria, Hungary, and Slovakia from 01 December 2017 to 06 September 2019.
Pre-assignment Detail	Participants with diagnosis of Type 2 Diabetes Mellitus were enrolled in 1 of 4 treatment groups: Placebo or Sotagliflozin 200 mg or Sotagliflozin 400 mg or Glimepiride. Participants were randomly assigned in the ratio of 1:1:2:2 to these reporting groups. Total of 954 participants were enrolled in study, out of which 952 were randomized and treated.

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
Period Title: Overall Study
STARTED	159	317	160	318
COMPLETED	125	266	128	270
NOT COMPLETED	34	51	32	48

Baseline Characteristics

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride	Total
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Total of all reporting groups
Overall Participants	159	317	160	318	954
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (11.2)	59.7 (10.4)	58.6 (9.9)	59.8 (9.6)	59.4 (10.2)
Sex: Female, Male (Count of Participants)
Female	77 48.4%	157 49.5%	75 46.9%	143 45%	452 47.4%
Male	82 51.6%	160 50.5%	85 53.1%	175 55%	502 52.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	48 30.2%	85 26.8%	53 33.1%	111 34.9%	297 31.1%
Not Hispanic or Latino	110 69.2%	230 72.6%	106 66.3%	207 65.1%	653 68.4%
Unknown or Not Reported	1 0.6%	2 0.6%	1 0.6%	0 0%	4 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.3%	0 0%	1 0.3%	2 0.2%
Asian	3 1.9%	5 1.6%	3 1.9%	4 1.3%	15 1.6%
Native Hawaiian or Other Pacific Islander	1 0.6%	1 0.3%	2 1.3%	0 0%	4 0.4%
Black or African American	13 8.2%	34 10.7%	19 11.9%	36 11.3%	102 10.7%
White	141 88.7%	269 84.9%	136 85%	277 87.1%	823 86.3%
More than one race	1 0.6%	3 0.9%	0 0%	0 0%	4 0.4%
Unknown or Not Reported	0 0%	4 1.3%	0 0%	0 0%	4 0.4%
Region of Enrollment (participants) [Number]
Bulgaria	7 4.4%	17 5.4%	5 3.1%	16 5%	45 4.7%
Hungary	22 13.8%	48 15.1%	24 15%	42 13.2%	136 14.3%
Slovakia	12 7.5%	28 8.8%	10 6.3%	30 9.4%	80 8.4%
United States	118 74.2%	224 70.7%	121 75.6%	230 72.3%	693 72.6%
Hemoglobin A1c (HbA1c) (percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of HbA1c]	8.12 (0.73)	8.09 (0.78)	8.11 (0.86)	8.07 (0.79)	8.09 (0.79)
Systolic Blood Pressure (SBP) (millimeter of mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeter of mercury (mmHg)]	133.23 (14.90)	133.17 (14.37)	132.78 (13.29)	134.66 (14.43)	133.61 (14.30)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c at Week 52
Description	An analysis of covariance (ANCOVA) model was used for the analysis.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Intend to treat (ITT) population included all randomized participants. Missing data are imputed using the retrieved dropouts imputation method.

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
Measure Participants	159	317	160	318
Least Squares Mean (Standard Error) [percentage of HbA1c]	-0.40 (0.187)	-0.65 (0.101)	-0.49 (0.114)	-0.61 (0.093)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Glimepiride
	Comments	The change from baseline to Week 52 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority hypothesis was declared significant if the upper bound of the 2-sided 95% confidence interval (CI) for the adjusted mean difference is <0.3.
Statistical Test of Hypothesis	p-Value	0.3306
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares (LS) Mean
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.120 to 0.357
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.122
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 200 mg, Glimepiride
	Comments	The change from baseline to Week 52 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority hypothesis was declared significant if the upper bound of the 2-sided 95% CI for the adjusted mean difference is <0.3.
Statistical Test of Hypothesis	p-Value	0.7112
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.265 to 0.181
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.114
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Hemoglobin A1c at Week 26
Description	An ANCOVA model was used for the analysis.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Missing data are imputed using the washout imputation method.

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
Measure Participants	159	317	160	318
Least Squares Mean (Standard Error) [percentage of HbA1c]	-0.41 (0.097)	-0.77 (0.076)	-0.61 (0.098)	-1.02 (0.075)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Glimepiride
	Comments	The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0827
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.440 to 0.027
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.119
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 200 mg, Glimepiride
	Comments	The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.571 to -0.167
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.103
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 26 and 52
Description	An ANCOVA model was used for the analysis.
Time Frame	Baseline, Week 26, Week 52

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Missing data are imputed using the retrieved dropouts & washout imputation method.

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
Measure Participants	159	317	160	318
Change at Week 26	-1.26 (0.329)	-2.75 (0.257)	-2.24 (0.336)	0.70 (0.256)
Change at Week 52	-0.47 (1.406)	-2.64 (0.503)	-1.74 (0.707)	0.94 (0.452)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups (placebo, sotagliflozin 200 mg, sotagliflozin 400 mg, glimepiride), randomization strata of HbA1c (≤ 8.5, >8.5%) at screening, randomization strata of SBP (<130,≥ 130 mmHg) at screening, and country as fixed effects, and baseline body weight as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-1.49
	Confidence Interval	(2-Sided) 95%; -2.173 to -0.803
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.349
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Glimepiride
	Comments	The change from baseline to Week 52 is analyzed using analysis of ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of SBP (<130, ≥130 mmHg) at screening, and country as fixed effects and baseline body weight as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-3.58
	Confidence Interval	(2-Sided) 95%; -4.651 to -2.517
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.544
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP ≥130 mmHg at Week 12
Description	An ANCOVA model was used for the analysis.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population in participants with baseline SBP ≥130 mmHg. Missing data are imputed using washout imputation method.

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
Measure Participants	79	161	81	175
Least Squares Mean (Standard Error) [mmHg]	-5.34 (1.451)	-8.03 (1.064)	-9.12 (1.466)	-3.86 (1.081)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Glimepiride
	Comments	The change from baseline to Week 12 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, and country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-4.18
	Confidence Interval	(2-Sided) 95%; -6.701 to -1.650
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.288
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 12 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, and country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0973
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-2.70
	Confidence Interval	(2-Sided) 95%; -5.890 to 0.491
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0973
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12
Description	An ANCOVA model was used for the analysis.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Missing data are imputed using washout imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
Measure Participants	159	317	160	318
Least Squares Mean (Standard Error) [mmHg]	-2.64 (1.013)	-4.70 (0.791)	-4.77 (1.033)	-0.68 (0.795)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Glimepiride
	Comments	The change from baseline to Week 12 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤ 8.5, >8.5%) at screening, and country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-4.02
	Confidence Interval	(2-Sided) 95%; -5.730 to -2.319
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.870
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event
Description	Documented symptomatic hypoglycemia includes the 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).
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
Measure Participants	159	317	160	318
Number [percentage of participants]	0.63 0.4%	1.26 0.4%	3.75 2.3%	16.67 5.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Glimepiride
	Comments	Weighted average of percentage difference between treatment groups from each stratum [randomization strata of HbA1c [≤8.5%, >8.5%] at screening, randomization strata of mean SBP [<130, ≥130 mmHg] at screening using Cochran-Mantel-Haenszel weights.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	-15.4
	Confidence Interval	(2-Sided) 95%; -19.67 to -11.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population included all participants who had received at least one dose of study drug.

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
Measure Participants	159	317	159	317
Number [percentage of participants]	57.2 36%	59.9 18.9%	56.6 35.4%	49.2 15.5%

8. Other Pre-specified Outcome

Title	Percentage of Participants With Hypoglycemic Events
Description	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].
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least 1 dose of double-blind investigational medicinal product (IMP) (regardless of the amount of treatment administered).

Arm/Group Title	Placebo	Sotagliflozin 400 mg	Sotagliflozin 200 mg	Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
Measure Participants	159	317	159	317
Any hypoglycemia	2.5 1.6%	4.1 1.3%	6.3 3.9%	25.9 8.1%
Documented symptomatic hypoglycemia	0.6 0.4%	1.3 0.4%	3.8 2.4%	16.7 5.3%
Severe or documented symptomatic hypoglycemia	0.6 0.4%	1.3 0.4%	3.8 2.4%	16.7 5.3%

Adverse Events

Time Frame	First dose of study drug to last dose of study drug (up to 52 weeks) + 2 weeks
Adverse Event Reporting Description	Safety population included all participants who had received at least one dose of study drug.
Arm/Group Title	Placebo		Sotagliflozin 400 mg		Sotagliflozin 200 mg		Glimepiride
Arm/Group Description	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.		Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.		Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.		Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
All Cause Mortality
	Placebo		Sotagliflozin 400 mg		Sotagliflozin 200 mg		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/159 (1.3%)		1/317 (0.3%)		0/159 (0%)		2/317 (0.6%)
Serious Adverse Events
	Placebo		Sotagliflozin 400 mg		Sotagliflozin 200 mg		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/159 (6.9%)		17/317 (5.4%)		11/159 (6.9%)		14/317 (4.4%)
Cardiac disorders
Acute left ventricular failure	1/159 (0.6%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Acute myocardial infarction	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		1/317 (0.3%)
Angina pectoris	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Angina unstable	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Atrial fibrillation	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Cardiac failure	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Coronary artery disease	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Supraventricular tachycardia	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Eye disorders
Retinal haemorrhage	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Gastrointestinal disorders
Diverticulum intestinal haemorrhagic	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Gastrointestinal inflammation	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Pancreatitis acute	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Small intestinal obstruction	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Umbilical hernia	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
General disorders
Death	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Incarcerated hernia	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Influenza like illness	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Non-cardiac chest pain	2/159 (1.3%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Sudden cardiac death	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Hepatobiliary disorders
Cholecystitis chronic	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Cholelithiasis	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Infections and infestations
Cholecystitis infective	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Epididymitis	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Erysipelas	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Gastroenteritis	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Pneumonia	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		2/317 (0.6%)
Pneumonia legionella	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Pyelonephritis chronic	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Sepsis	0/159 (0%)		1/317 (0.3%)		1/159 (0.6%)		1/317 (0.3%)
Urinary tract infection	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		1/317 (0.3%)
Injury, poisoning and procedural complications
Ankle fracture	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Concussion	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Fall	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Femur fracture	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Fibula fracture	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Hand fracture	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Intentional overdose	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Joint dislocation	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Road traffic accident	0/159 (0%)		1/317 (0.3%)		1/159 (0.6%)		1/317 (0.3%)
Tibia fracture	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Vascular graft stenosis	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Metabolism and nutrition disorders
Dehydration	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Gout	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Intervertebral disc protrusion	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		1/317 (0.3%)
Musculoskeletal chest pain	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Osteoarthritis	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Vertebral osteophyte	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Basal cell carcinoma	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Bladder transitional cell carcinoma	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Breast cancer	1/159 (0.6%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Oesophageal adenocarcinoma	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Prostate cancer	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Squamous cell carcinoma	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Nervous system disorders
Cerebellar stroke	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Hemiparesis	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Syncope	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Transient ischaemic attack	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Psychiatric disorders
Alcohol withdrawal syndrome	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Depression	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Suicide attempt	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Reproductive system and breast disorders
Adnexa uteri mass	0/159 (0%)		1/317 (0.3%)		0/159 (0%)		0/317 (0%)
Metrorrhagia	0/159 (0%)		0/317 (0%)		0/159 (0%)		1/317 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Vascular disorders
Hypertension	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Hypertensive crisis	1/159 (0.6%)		0/317 (0%)		0/159 (0%)		0/317 (0%)
Vasculitis	0/159 (0%)		0/317 (0%)		1/159 (0.6%)		0/317 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Sotagliflozin 400 mg		Sotagliflozin 200 mg		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/159 (18.9%)		49/317 (15.5%)		21/159 (13.2%)		22/317 (6.9%)
Gastrointestinal disorders
Diarrhoea	11/159 (6.9%)		14/317 (4.4%)		8/159 (5%)		7/317 (2.2%)
Infections and infestations
Vulvovaginal mycotic infection	2/159 (1.3%)		19/317 (6%)		6/159 (3.8%)		2/317 (0.6%)
Metabolism and nutrition disorders
Hyperglycaemia	8/159 (5%)		5/317 (1.6%)		2/159 (1.3%)		2/317 (0.6%)
Nervous system disorders
Headache	11/159 (6.9%)		14/317 (4.4%)		7/159 (4.4%)		12/317 (3.8%)

Limitations/Caveats

[Not Specified]

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

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.