SOTA-INS: Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking Insulin Alone or With Other Oral Antidiabetic Agents

• Sponsor: Lexicon Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03285594
• Collaborator: Sanofi (Industry)
• Enrollment: 571
• Locations: 106
• Arms: 3
• Actual Duration (Months): 24.4
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate the superiority of sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1C (HbA1c) reduction in participants with type 2 diabetes mellitus (T2D) who have inadequate glycemic control on basal insulin alone or with oral antidiabetes drugs (OADs).

Secondary Objectives:

• To assess the effects of sotagliflozin 400 mg versus placebo on fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), and HbA1c.

• To assess the effects of sotagliflozin 200 mg versus placebo on HbA1c, body weight, FPG, and SBP.

• To evaluate the safety of sotagliflozin 400 and 200 mg versus placebo.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Sotagliflozin; Drug: Insulin glargine (HOE901); Drug: Placebo; Drug: Oral Antidiabetes Drugs (OADs)	Phase 3

Detailed Description

Up to 60 weeks (Screening phase of up to 2 weeks, a 4-week Lantus titration/single-blind placebo Run-in phase), a 52-week double blind Treatment Period, and a 2-week post-treatment Follow-up Period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 571 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Alone or in Addition to Oral Antidiabetes Drugs (OADs)
• Actual Study Start Date: Sep 15, 2017
• Actual Primary Completion Date: Sep 17, 2019
• Actual Study Completion Date: Sep 27, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Following a 4-week run-in period, participants were randomized to matching placebo to sotagliflozin 200 milligrams (mg) administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Drug: Insulin glargine (HOE901); Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: Lantus ; Drug: Placebo; Pharmaceutical form: Tablet Route of administration: Oral; Drug: Oral Antidiabetes Drugs (OADs); OADs (including metformin) as prescribed by the investigator as per local labeling.
Experimental: Sotagliflozin 200 mg Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Drug: Sotagliflozin; Pharmaceutical form: Tablet Route of administration: Oral; Other Names: SAR439954 ; Drug: Insulin glargine (HOE901); Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: Lantus ; Drug: Placebo; Pharmaceutical form: Tablet Route of administration: Oral; Drug: Oral Antidiabetes Drugs (OADs); OADs (including metformin) as prescribed by the investigator as per local labeling.
Experimental: Sotagliflozin 400 mg Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Drug: Sotagliflozin; Pharmaceutical form: Tablet Route of administration: Oral; Other Names: SAR439954 ; Drug: Insulin glargine (HOE901); Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: Lantus ; Drug: Oral Antidiabetes Drugs (OADs); OADs (including metformin) as prescribed by the investigator as per local labeling.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18 [Baseline and Week 18]

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

Secondary Outcome Measures

1. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 [Baseline and Week 18]

   FPG was performed in fasting state, that is, without any food intake (except for water) for at least 8 hours. An ANCOVA model was used for the analysis.

2. Change From Baseline in Body Weight at Week 18 [Baseline and Week 18]

   An ANCOVA model was used for the analysis.

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

   An ANCOVA model was used for the analysis. Here, N is the number of participants with data available at a given time point.

4. Change From Baseline in SBP at Week 12 for All Participants [Baseline to Week 12]

   An ANCOVA model was used for the analysis.

5. Change From Baseline in HbA1c at Week 52 [Baseline and Week 52]

   An ANCOVA model was used for the analysis.

6. Change From Baseline in Body Weight at Week 52 [Baseline and Week 52]

   An ANCOVA model was used for the analysis.

7. Percentage of Participants With Adverse Events (AEs) [First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 weeks]

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

Other Outcome Measures

1. Percentage of Participants With Hypoglycemic Events [Up to 55.7 weeks]

   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 Mellitus (T2DM) using any types of basal insulin alone or in combination with up to 2 OADs.

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

Exclusion criteria:

• At the time of Screening age <18 years or <legal age of majority, whichever is greater.

• Type 1 diabetes mellitus.

• Oral antidiabetic drugs dose not stable for 8 weeks before Screening.

• Use of basal insulin therapy (e.g., insulin glargine, Neutral Protamine Hagedorn (NPH), detemir, or degludec) for less than 6 months before Screening.

• Dose of basal insulin (e.g., insulin glargine, NPH, detemir, or degludec) not stable for 8 weeks before Screening (i.e., total daily insulin dose increased or decreased by more than 20%).

• Known unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema that is likely to require laser, surgical treatment during study period.

• Use of injectable diabetes drugs other than basal insulin (e.g., insulin glargine, NPH, detemir, or degludec), i.e., prandial or rapid-acting insulins, short-acting insulins, glucagon-like peptide 1 (GLP-1) receptor agonists, or inhaled prandial insulin (Afrezza) within 8 weeks of Screening.

• Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the trial.

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

• 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 the Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.

• Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization.

• Known presence of factors that interfere with the Central Lab HbA1c measurement (e.g., genetic hemoglobin (Hb) variants) compromising the reliability of HbA1c assessment or medical conditions that affect interpretation of HbA1c results (e.g., blood transfusion or severe blood loss in the last 3 months prior to randomization, any condition that shortens erythrocyte survival).

• Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from prior to Screening, whichever is longer.

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

• HbA1c <7.5% or HbA1c >10.5% measured by the central laboratory at Screening.

• HbA1c <7% measured by the central laboratory at Visit 5 (Week -1).

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

• Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.

• Women of childbearing potential 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 during the study.

• Mean of 3 separate blood pressure measurements >180 mmHg (systolic blood pressure [SBP]) or >100 mmHg (diastolic blood pressure [DBP]).

• History of gastric surgery including history of gastric banding or inflammatory bowel disease within 3 years prior to the Screening Visit.

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of the normal laboratory range

• Total bilirubin >1.5 times the upper limit of the normal laboratory range (except in case of Gilbert's syndrome).

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 8406028	Mesa	Arizona	United States	85213-5226
2	Investigational Site Number 8406013	Phoenix	Arizona	United States	85018
3	Investigational Site Number 8406020	Phoenix	Arizona	United States	85020
4	Investigational Site Number 8406006	Huntington Park	California	United States	90255
5	Investigational Site Number 8406053	Lincoln	California	United States	95648
6	Investigational Site Number 8406040	Los Angeles	California	United States	90057
7	Investigational Site Number 8406043	Coral Gables	Florida	United States	33134
8	Investigational Site Number 8406008	DeLand	Florida	United States	32720
9	Investigational Site Number 8406030	Maitland	Florida	United States	32751
10	Investigational Site Number 8406003	New Port Richey	Florida	United States	34652
11	Investigational Site Number 8406029	North Miami Beach	Florida	United States	33162
12	Investigational Site Number 8406052	Ocoee	Florida	United States	34761
13	Investigational Site Number 8406001	Port Charlotte	Florida	United States	33952
14	Investigational Site Number 8406022	Saint Petersburg	Florida	United States	33700
15	Investigational Site Number 8406025	Tampa	Florida	United States	33634
16	Investigational Site Number 8406002	West Palm Beach	Florida	United States	33401-3430
17	Investigational Site Number 8406054	Chicago	Illinois	United States	60602
18	Investigational Site Number 8406027	Chicago	Illinois	United States	60604
19	Investigational Site Number 8406042	Evansville	Indiana	United States	47714
20	Investigational Site Number 8406044	New Orleans	Louisiana	United States	70119-6302
21	Investigational Site Number 8406051	New Orleans	Louisiana	United States	70124
22	Investigational Site Number 8406024	Rockville	Maryland	United States	20852
23	Investigational Site Number 8406016	Detroit	Michigan	United States	48202
24	Investigational Site Number 8406011	Saint Louis	Missouri	United States	63110
25	Investigational Site Number 8406010	Papillion	Nebraska	United States	68046-3136
26	Investigational Site Number 8406018	New York	New York	United States	10016-6023
27	Investigational Site Number 8406034	Asheville	North Carolina	United States	28803
28	Investigational Site Number 8406046	Chapel Hill	North Carolina	United States	27517
29	Investigational Site Number 8406026	Charlotte	North Carolina	United States	28209
30	Investigational Site Number 8406038	Greenville	North Carolina	United States	27834
31	Investigational Site Number 8406036	Hickory	North Carolina	United States	28601
32	Investigational Site Number 8406015	Wilmington	North Carolina	United States	28401-6638
33	Investigational Site Number 8406019	Winston-Salem	North Carolina	United States	27103
34	Investigational Site Number 8406031	Beachwood	Ohio	United States	44122
35	Investigational Site Number 8406023	Columbus	Ohio	United States	43201
36	Investigational Site Number 8406005	Dublin	Ohio	United States	43016
37	Investigational Site Number 8406004	Mentor	Ohio	United States	44060
38	Investigational Site Number 8406033	Oklahoma City	Oklahoma	United States	73111
39	Investigational Site Number 8406032	Moncks Corner	South Carolina	United States	29461-5017
40	Investigational Site Number 8406009	Chattanooga	Tennessee	United States	37421
41	Investigational Site Number 8406045	Seymour	Tennessee	United States	37865-5270
42	Investigational Site Number 8406047	Dallas	Texas	United States	75230
43	Investigational Site Number 8406017	Dallas	Texas	United States	75231
44	Investigational Site Number 8406048	Houston	Texas	United States	77079
45	Investigational Site Number 8406037	Houston	Texas	United States	77099
46	Investigational Site Number 8406039	McAllen	Texas	United States	78504
47	Investigational Site Number 8406050	San Antonio	Texas	United States	78229
48	Investigational Site Number 8406021	Shavano Park	Texas	United States	78231
49	Investigational Site Number 8406035	Salt Lake City	Utah	United States	84102-1553
50	Investigational Site Number 8406014	West Jordan	Utah	United States	84088-8865
51	Investigational Site Number 1006009	Gabrovo		Bulgaria	5300
52	Investigational Site Number 1006003	Plovdiv		Bulgaria	4002
53	Investigational Site Number 1006004	Ruse		Bulgaria	7002
54	Investigational Site Number 1006001	Ruse		Bulgaria	7003
55	Investigational Site Number 1006006	Smolyan		Bulgaria	4700
56	Investigational Site Number 1006002	Sofia		Bulgaria	1606
57	Investigational Site Number 1006010	Sofia		Bulgaria	1750
58	Investigational Site Number 1006005	Stara Zagora		Bulgaria	6000
59	Investigational Site Number 1006007	Varna		Bulgaria	9000
60	Investigational Site Number 1246003	Brampton		Canada	L6S 0C9
61	Investigational Site Number 1246005	Burlington		Canada	L7R 1E2
62	Investigational Site Number 1246004	Etobicoke		Canada	M9R 4E1
63	Investigational Site Number 1246002	Toronto		Canada	M4G 3E8
64	Investigational Site Number 1246001	Vancouver		Canada	V5Y 3W2
65	Investigational Site Number 2036003	Holesov		Czechia	769 01
66	Investigational Site Number 2036002	Krnov		Czechia	794 01
67	Investigational Site Number 2036001	Olomouc		Czechia	779 00
68	Investigational Site Number 2036005	Ostrava		Czechia	702 00
69	Investigational Site Number 2036006	Praha 10 - Uhrineves		Czechia	104 00
70	Investigational Site Number 2036007	Praha 4		Czechia	140 46
71	Investigational Site Number 2036008	Praha 4		Czechia	149 00
72	Investigational Site Number 2506008	Besançon Cedex		France	25030
73	Investigational Site Number 2506003	Corbeil-Essonnes		France	91106
74	Investigational Site Number 2506005	Dijon		France	21079
75	Investigational Site Number 2506012	Mulhouse		France	68100
76	Investigational Site Number 2506004	Nantes		France	44093
77	Investigational Site Number 2506007	Narbonne		France	11100
78	Investigational Site Number 2506006	Paris		France	75018
79	Investigational Site Number 2506010	Pierre-Benite		France	69495
80	Investigational Site Number 2506009	Poitiers		France	86021
81	Investigational Site Number 2506011	Saint-Mande		France	94160
82	Investigational Site Number 2506002	Vénissieux		France	69200
83	Investigational Site Number 3486007	Budapest		Hungary	1106
84	Investigational Site Number 3486002	Budapest		Hungary	1134
85	Investigational Site Number 3486006	Hatvan		Hungary	3000
86	Investigational Site Number 3486009	Kecskemet		Hungary	6000
87	Investigational Site Number 3486003	Komarom		Hungary	2900
88	Investigational Site Number 3486005	Nyíregyháza		Hungary	4400
89	Investigational Site Number 3486001	Pécs		Hungary	7623
90	Investigational Site Number 3486008	Zalaegerszeg		Hungary	8900
91	Investigational Site Number 7036004	Bardejov		Slovakia	085 01
92	Investigational Site Number 7036008	Bratislava		Slovakia	831 06
93	Investigational Site Number 7036001	Bratislava		Slovakia	85101
94	Investigational Site Number 7036010	Kosice		Slovakia	040 01
95	Investigational Site Number 7036003	Kosice		Slovakia	4014
96	Investigational Site Number 7036007	Levice		Slovakia	934 01
97	Investigational Site Number 7036009	Levice		Slovakia	934 05
98	Investigational Site Number 7036011	Lucenec		Slovakia	98401
99	Investigational Site Number 7036006	Nitra		Slovakia	949 11
100	Investigational Site Number 7036005	Sabinov		Slovakia	08301
101	Investigational Site Number 8266002	Darlington		United Kingdom	DL3 6HX
102	Investigational Site Number 8266006	Doncaster		United Kingdom	DN9 2HY
103	Investigational Site Number 8266008	Dundee		United Kingdom	DD1 9SY
104	Investigational Site Number 8266001	Leicester		United Kingdom	LE5 4PW
105	Investigational Site Number 8266004	London		United Kingdom	EC1M 6BQ
106	Investigational Site Number 8266003	Salford		United Kingdom	M6 8HD

Sponsors and Collaborators

• Lexicon Pharmaceuticals
• Sanofi

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Mar 12, 2018
• Statistical Analysis Plan - Dec 5, 2019

More Information

Publications

None provided.

• Responsible Party: Lexicon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03285594
• Other Study ID Numbers: EFC14868; 2016-001804-43; U1111-1190-7567
• First Posted: Sep 18, 2017
• Last Update Posted: May 11, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Glargine; (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 101 investigative sites in the United States, Bulgaria, Canada, Czech Republic, France, Hungary, Slovakia, the United Kingdom from 15 September 2017 to 27 September 2019.
Pre-assignment Detail	Participants with a diagnosis of Type 2 Diabetes Mellitus were enrolled in 1 of 3 treatment groups, placebo, sotagliflozin 200 milligrams (mg) and sotagliflozin 400 mg. Participants were randomized at a ratio of 1:1:2 respectively to 1 of 3 groups.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without oral antidiabetes drugs [OADs]) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Period Title: Overall Study
STARTED	144	141	286
Treated	144	141	285
COMPLETED	129	130	249
NOT COMPLETED	15	11	37

Baseline Characteristics

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg	Total
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Total of all reporting groups
Overall Participants	144	141	286	571
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.2 (8.9)	62.1 (10.2)	62.7 (9.1)	62.4 (9.4)
Sex: Female, Male (Count of Participants)
Female	58 40.3%	65 46.1%	132 46.2%	255 44.7%
Male	86 59.7%	76 53.9%	154 53.8%	316 55.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 8.3%	25 17.7%	42 14.7%	79 13.8%
Not Hispanic or Latino	129 89.6%	113 80.1%	239 83.6%	481 84.2%
Unknown or Not Reported	3 2.1%	3 2.1%	5 1.7%	11 1.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1.4%	1 0.7%	2 0.7%	5 0.9%
Asian	9 6.3%	1 0.7%	6 2.1%	16 2.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	3 1%	3 0.5%
Black or African American	10 6.9%	10 7.1%	27 9.4%	47 8.2%
White	117 81.3%	124 87.9%	234 81.8%	475 83.2%
More than one race	1 0.7%	0 0%	1 0.3%	2 0.4%
Unknown or Not Reported	5 3.5%	5 3.5%	13 4.5%	23 4%
Region of Enrollment (participants) [Number]
Bulgaria	9 6.3%	13 9.2%	35 12.2%	57 10%
Canada	7 4.9%	6 4.3%	16 5.6%	29 5.1%
Czechia	14 9.7%	11 7.8%	24 8.4%	49 8.6%
France	8 5.6%	8 5.7%	14 4.9%	30 5.3%
Hungary	12 8.3%	13 9.2%	21 7.3%	46 8.1%
Slovakia	24 16.7%	21 14.9%	32 11.2%	77 13.5%
United Kingdom	0 0%	0 0%	4 1.4%	4 0.7%
United States	70 48.6%	69 48.9%	140 49%	279 48.9%
Hemoglobin A1c (HbA1c) (percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of HbA1c]	8.76 (0.79)	8.76 (0.83)	8.69 (0.80)	8.72 (0.80)
Systolic Blood Pressure (SBP) (millimeter of Mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeter of Mercury (mmHg)]	137.59 (14.12)	136.40 (15.54)	135.84 (14.95)	136.42 (14.89)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18
Description	An analysis of covariance (ANCOVA) model was used for the analysis.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Measure Participants	144	141	286
Least Squares Mean (Standard Error) [percentage of HbA1c]	-0.27 (0.073)	-0.72 (0.073)	-0.81 (0.056)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline HbA1c 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 Least Square (LS) Means
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -0.638 to -0.271
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.094
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline HbA1c 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 Means
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95%; -0.706 to -0.387
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.081
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18
Description	FPG was performed in fasting state, that is, without any food intake (except for water) for at least 8 hours. An ANCOVA model was used for the analysis.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Measure Participants	144	141	286
Least Squares Mean (Standard Error) [milligram per deciliter (mg/dL)]	12.882 (3.6045)	-2.975 (3.6083)	-8.949 (2.7550)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline FPG as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-15.858
	Confidence Interval	(2-Sided) 95%; -24.8845 to -6.8309
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.6056
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline FPG 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 Means
	Estimated Value	-21.832
	Confidence Interval	(2-Sided) 95%; -29.7725 to -13.8911
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.0514
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 18
Description	An ANCOVA model was used for the analysis.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Measure Participants	144	141	286
Least Squares Mean (Standard Error) [kilogram (kg)]	0.36 (0.249)	-0.73 (0.250)	-1.37 (0.190)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 18 is analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline body weight as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-1.09
	Confidence Interval	(2-Sided) 95%; -1.716 to -0.462
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 18 is analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, 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 Means
	Estimated Value	-1.73
	Confidence Interval	(2-Sided) 95%; -2.274 to -1.183
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.278
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12
Description	An ANCOVA model was used for the analysis. Here, N is the number of participants with data available at a given time point.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Analysis population included participants with baseline SBP ≥ 130 mmHg in ITT population where, ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Measure Participants	88	92	171
Least Squares Mean (Standard Error) [mmHg]	-4.67 (1.470)	-8.58 (1.447)	-8.50 (1.103)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-3.91
	Confidence Interval	(2-Sided) 95%; -7.642 to -0.178
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.904
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0239
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-3.83
	Confidence Interval	(2-Sided) 95%; -7.161 to -0.507
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.697
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in SBP at Week 12 for All Participants
Description	An ANCOVA model was used for the analysis.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Measure Participants	144	141	286
Least Squares Mean (Standard Error) [mmHg]	-0.21 (1.120)	-5.15 (1.117)	-4.10 (0.867)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-4.94
	Confidence Interval	(2-Sided) 95%; -7.73 to -2.142
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.425
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-3.89
	Confidence Interval	(2-Sided) 95%; -6.333 to -1.448
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.246
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in HbA1c at Week 52
Description	An ANCOVA model was used for the analysis.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Measure Participants	144	141	286
Least Squares Mean (Standard Error) [percentage of HbA1c]	0.00 (0.279)	-0.52 (0.152)	-0.57 (0.114)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 52 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline HbA1c as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1265
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -1.185 to 0.147
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 52 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline HbA1c as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.074
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -1.199 to 0.055
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Measure Participants	144	141	286
Least Squares Mean (Standard Error) [kg]	-0.18 (0.579)	-1.19 (0.620)	-0.83 (0.374)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline body weight as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2466
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) 95%; -2.707 to 0.696
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.868
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline body weight as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.332
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95%; -1.969 to 0.665
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.672
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	An AE is any untoward medical occurrence in a participants or clinical investigation participants administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame	First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 weeks

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 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Measure Participants	144	141	285
Number [percentage of participants]	64.6 44.9%	54.6 38.7%	59.3 20.7%

9. 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 55.7 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all randomised 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 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without oral antidiabetes drugs [OADs]) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Measure Participants	144	141	285
Any hypoglycemia	62.5 43.4%	56.0 39.7%	62.8 22%
Documented symptomatic hypoglycemia	44.4 30.8%	41.8 29.6%	46 16.1%
Severe or documented symptomatic hypoglycemia	44.4 30.8%	41.8 29.6%	46 16.1%

Adverse Events

Time Frame	Deaths: Up to approximately 60 weeks; Adverse Events: First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 weeks
Adverse Event Reporting Description	Safety population included all randomized participants who had received at least 1 dose of double-blind investigational medicinal product (regardless of the amount of treatment administered). Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
Arm/Group Title	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
Arm/Group Description	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.		Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.		Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
All Cause Mortality
	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/144 (1.4%)		1/141 (0.7%)		6/285 (2.1%)
Serious Adverse Events
	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/144 (11.1%)		19/141 (13.5%)		28/285 (9.8%)
Cardiac disorders
Acute myocardial infarction	2/144 (1.4%)		0/141 (0%)		2/285 (0.7%)
Angina unstable	1/144 (0.7%)		1/141 (0.7%)		0/285 (0%)
Atrial fibrillation	3/144 (2.1%)		0/141 (0%)		0/285 (0%)
Atrial flutter	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Cardiac arrest	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Cardiac failure	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Cardiac failure acute	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Cardiac failure congestive	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Cardiogenic shock	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Coronary artery disease	0/144 (0%)		0/141 (0%)		2/285 (0.7%)
Ischaemic cardiomyopathy	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Left ventricular failure	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Myocardial infarction	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Myocardial ischaemia	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Reperfusion arrhythmia	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Ear and labyrinth disorders
Vertigo	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Eye disorders
Retinal artery thrombosis	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Retinopathy proliferative	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Gastrointestinal disorders
Pancreatitis acute	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Pancreatitis chronic	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Enlarged uvula	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
General disorders
Death	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Non-cardiac chest pain	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Sudden cardiac death	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Hepatobiliary disorders
Biliary dyskinesia	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Cholangitis	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Infections and infestations
Gastroenteritis	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Infected bite	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Localised infection	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Osteomyelitis	1/144 (0.7%)		0/141 (0%)		1/285 (0.4%)
Osteomyelitis acute	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Postoperative wound infection	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Pyelonephritis chronic	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Renal abscess	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Scrotal abscess	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Urinary tract infection	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Injury, poisoning and procedural complications
Jaw fracture	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Multiple injuries	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Postoperative thrombosis	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Subdural haematoma	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Tendon injury	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Tibia fracture	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Investigations
Alanine aminotransferase increased	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Diabetic ketoacidosis	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Diabetic metabolic decompensation	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Hyperglycaemia	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Hyperkalaemia	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Hypoglycaemia	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/144 (0%)		2/141 (1.4%)		0/285 (0%)
Rheumatoid arthritis	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Spinal pain	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Bursitis	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
B-cell lymphoma	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Basal cell carcinoma	1/144 (0.7%)		1/141 (0.7%)		0/285 (0%)
Bladder cancer	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Lung cancer metastatic	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Metastases to bone	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Prostate cancer	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Squamous cell carcinoma	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Transitional cell carcinoma	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Nervous system disorders
Cervicobrachial syndrome	1/144 (0.7%)		0/141 (0%)		0/285 (0%)
Hypoglycaemic unconsciousness	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Syncope	1/144 (0.7%)		1/141 (0.7%)		1/285 (0.4%)
Transient ischaemic attack	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Renal and urinary disorders
Nephrolithiasis	1/144 (0.7%)		0/141 (0%)		1/285 (0.4%)
Renal haematoma	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Urethral stenosis	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Pulmonary oedema	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Respiratory failure	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Sleep apnoea syndrome	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Vascular disorders
Aortic stenosis	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Hypertension	0/144 (0%)		0/141 (0%)		1/285 (0.4%)
Peripheral arterial occlusive disease	0/144 (0%)		1/141 (0.7%)		0/285 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/144 (20.8%)		18/141 (12.8%)		45/285 (15.8%)
Infections and infestations
Nasopharyngitis	7/144 (4.9%)		9/141 (6.4%)		14/285 (4.9%)
Upper respiratory tract infection	8/144 (5.6%)		1/141 (0.7%)		14/285 (4.9%)
Urinary tract infection	8/144 (5.6%)		6/141 (4.3%)		11/285 (3.9%)
Metabolism and nutrition disorders
Vitamin D deficiency	9/144 (6.3%)		4/141 (2.8%)		10/285 (3.5%)

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.