SOTA-EMPA: Efficacy and Safety of Sotagliflozin Versus Placebo and Empagliflozin in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking a DPP4 Inhibitor Alone or With Metformin

• Sponsor: Lexicon Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03351478
• Collaborator: Sanofi (Industry)
• Enrollment: 770
• Locations: 160
• Arms: 3
• Actual Duration (Months): 17.6
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of the study is to demonstrate the superiority of sotagliflozin versus placebo on hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control on a DPP4(i) with or without metformin.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Sotagliflozin; Drug: Empagliflozin; Drug: Placebo; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 770 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 26-week Randomized, Double-blind, Controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Compared to Empagliflozin, and Placebo in Participants With Type 2 Diabetes Who Have Inadequate Glycemic Control on Dipeptidyl Peptidase 4 Inhibitor (DPP4(i)) With or Without Metformin
• Actual Study Start Date: Nov 27, 2017
• Actual Primary Completion Date: May 16, 2019
• Actual Study Completion Date: May 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sotagliflozin 400 mg Following a 2-week run-in period, sotagliflozin 400 mg (milligrams) administered as two 200 mg tablets and one placebo capsule (identical to the empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Drug: Sotagliflozin; Sotagliflozin 400 mg was administered as two tablets, once daily before the first meal of the day.; Other Names: SAR439954 ; Drug: Placebo; Placebo was administered as one capsule (identical to the empagliflozin capsule in appearance), once daily before the first meal of the day.
Active Comparator: Empagliflozin 25 mg Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Drug: Empagliflozin; Empagliflozin 25 mg capsule was administered, once daily before the first meal of the day.; Drug: Placebo; Placebo was administered as two tablets (identical to sotagliflozin in appearance), once daily before the first meal of the day.
Placebo Comparator: Placebo Following a 2-week run-in period, placebo was given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.	Drug: Placebo; Placebo was administered as two tablets (identical to sotagliflozin in appearance), once daily before the first meal of the day.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hemoglobin A1c (HbA1c) % at Week 26 [Baseline, Week 26]

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

Secondary Outcome Measures

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

   An ANCOVA model was used for the analysis.

2. Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26 [Baseline, Week 26]

   An ANCOVA model was used for the analysis.

3. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 [Baseline, Week 26]

   An ANCOVA model was used for the analysis.

4. Change From Baseline in Body Weight at Week 26 [Baseline, Week 26]

   An ANCOVA model was used for the analysis.

5. Change From Baseline in Sitting SBP at Week 12 for All Participants [Baseline, Week 12]

   An ANCOVA model was used for the analysis.

6. Percentage of Participants With HbA1c <6.5% at Week 26 [Week 26]

7. Percentage of Participants With HbA1c <7.0% at Week 26 [Week 26]

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 on Dipeptidyl peptidase-4 inhibitors(DPP4(i)) with or without metformin at a stable dose for at least 12 weeks prior to Screening Visit. Metformin dose will be ≥1500 mg per day (or maximum tolerated dose [documented]). DPP4(i) dose must be the appropriate dose as per local label.

• Signed written informed consent.

Exclusion criteria:

• Body mass index (BMI) ≤20 kg/m^{2 or >45 kg/m}2 at Screening.

• Use of any antidiabetic drug other than DPP4 inhibitors and metformin within 12 weeks preceding the Screening Visit.

• Participants who have previously participated in any clinical trial of sotagliflozin/LX4211.

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

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

• Current diagnosis of chronic hepatitis and/or other clinically active liver disease requiring treatment.

• Participants with contraindication to empagliflozin as per local labelling.

• Participants with contraindication to metformin as per local labelling.

• Hemoglobin A1c <7.0% or >11.0% at Screening (central laboratory).

• Fasting plasma glucose >270 mg/dL (>15.0 mmol/L) measured by the central laboratory at Screening (Visit 1), and confirmed by a repeat test (>270 mg/dL [>15.0 mmol/L]) before Randomization.

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

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

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

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

• History of the hypertensive crisis resulting in emergency medical care within 12 weeks prior to Screening Visit.

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

• Laboratory findings with the central laboratory tests at Visit 1:

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

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

• Neutrophils <1 500/mm^{3 (or according to ethnic group) and/or platelets <100 000/mm}3;

• Amylase and/or lipase >3 times the ULN;

• Participants with renal impairment as defined by the estimated glomerular filtration rate (eGFR) criterion that precludes initiation of empagliflozin as per the approved local label (eg, <45 mL/min/1.73 m^{2 in US; <60 mL/min/1.73 m}2 in EU).

• Secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).

• If the participant is on hypertensive medications, the antihypertensive has been changed in the 8 weeks prior to Screening (new drug or new dose).

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 8408035	Birmingham	Alabama	United States	35205
2	Investigational Site Number 8408028	Sheffield	Alabama	United States	35660
3	Investigational Site Number 8408047	Hawaiian Gardens	California	United States	90716
4	Investigational Site Number 8408031	Spring Valley	California	United States	91978
5	Investigational Site Number 8408067	Van Nuys	California	United States	91405
6	Investigational Site Number 8408069	Northglenn	Colorado	United States	80234
7	Investigational Site Number 8408009	Miami	Florida	United States	33183-4825
8	Investigational Site Number 8408049	Ocoee	Florida	United States	34761
9	Investigational Site Number 8408005	Orlando	Florida	United States	32810
10	Investigational Site Number 8408040	Orlando	Florida	United States	32825
11	Investigational Site Number 8408019	Palmetto Bay	Florida	United States	33157-5503
12	Investigational Site Number 8408064	Port Charlotte	Florida	United States	33952
13	Investigational Site Number 8408061	Columbus	Georgia	United States	31904
14	Investigational Site Number 8408074	Macon	Georgia	United States	31210
15	Investigational Site Number 8408079	Savannah	Georgia	United States	31406
16	Investigational Site Number 8408059	Statesboro	Georgia	United States	30461-0845
17	Investigational Site Number 8408051	Blackfoot	Idaho	United States	83221
18	Investigational Site Number 8408033	Elgin	Illinois	United States	60124
19	Investigational Site Number 8408003	New Orleans	Louisiana	United States	70124
20	Investigational Site Number 8408002	Rockville	Maryland	United States	20852
21	Investigational Site Number 8408044	Fall River	Massachusetts	United States	02721-3005
22	Investigational Site Number 8408008	Flint	Michigan	United States	48532
23	Investigational Site Number 8408027	West Seneca	New York	United States	14224
24	Investigational Site Number 8408037	Fayetteville	North Carolina	United States	28314
25	Investigational Site Number 8408053	Greensboro	North Carolina	United States	27408-7042
26	Investigational Site Number 8408012	Greensboro	North Carolina	United States	27408
27	Investigational Site Number 8408013	Salisbury	North Carolina	United States	28144-2742
28	Investigational Site Number 8408045	Oklahoma City	Oklahoma	United States	73104-3252
29	Investigational Site Number 8408068	Warwick	Rhode Island	United States	02888-3360
30	Investigational Site Number 8408060	Fort Mill	South Carolina	United States	29707-4514
31	Investigational Site Number 8408018	Jefferson City	Tennessee	United States	37760
32	Investigational Site Number 8408010	Knoxville	Tennessee	United States	37912-4707
33	Investigational Site Number 8408038	Knoxville	Tennessee	United States	37938
34	Investigational Site Number 8408072	Brownsville	Texas	United States	78520-7512
35	Investigational Site Number 8408056	Dallas	Texas	United States	75208
36	Investigational Site Number 8408082	Dallas	Texas	United States	75230
37	Investigational Site Number 8408052	Dallas	Texas	United States	75231
38	Investigational Site Number 8408001	Houston	Texas	United States	77004
39	Investigational Site Number 8408032	Houston	Texas	United States	77004
40	Investigational Site Number 8408016	Houston	Texas	United States	77040
41	Investigational Site Number 8408017	Houston	Texas	United States	77058
42	Investigational Site Number 8408036	Houston	Texas	United States	77061
43	Investigational Site Number 8408022	Houston	Texas	United States	77099
44	Investigational Site Number 8408029	Katy	Texas	United States	77450
45	Investigational Site Number 8408054	McAllen	Texas	United States	78504
46	Investigational Site Number 8408039	Mesquite	Texas	United States	75149
47	Investigational Site Number 8408042	Plano	Texas	United States	75024
48	Investigational Site Number 8408011	San Antonio	Texas	United States	78229-3818
49	Investigational Site Number 8408041	Schertz	Texas	United States	78154
50	Investigational Site Number 8408007	Bountiful	Utah	United States	84010-7717
51	Investigational Site Number 8408026	Holladay	Utah	United States	84117
52	Investigational Site Number 8408006	Burke	Virginia	United States	22015
53	Investigational Site Number 8408004	Manassas	Virginia	United States	20110
54	Investigational Site Number 1008011	Gabrovo		Bulgaria	5300
55	Investigational Site Number 1008006	Plovdiv		Bulgaria	4000
56	Investigational Site Number 1008001	Plovdiv		Bulgaria	4002
57	Investigational Site Number 1008005	Ruse		Bulgaria	7002
58	Investigational Site Number 1008007	Ruse		Bulgaria	7003
59	Investigational Site Number 1008002	Smolyan		Bulgaria	4700
60	Investigational Site Number 1008008	Sofia		Bulgaria	1606
61	Investigational Site Number 1008012	Sofia		Bulgaria	1632
62	Investigational Site Number 1008003	Stara Zagora		Bulgaria	6000
63	Investigational Site Number 1008010	Stara Zagora		Bulgaria	6000
64	Investigational Site Number 1008004	Varna		Bulgaria	9000
65	Investigational Site Number 1248001	Brampton		Canada	L6T 0G1
66	Investigational Site Number 1248007	Burlington		Canada	L7M 4Y1
67	Investigational Site Number 1248003	Newmarket		Canada	L3Y 5G8
68	Investigational Site Number 1248010	Quebec		Canada	G1N 4V3
69	Investigational Site Number 1248009	Sherbrooke		Canada	J1L 0H8
70	Investigational Site Number 1248002	Thornhill		Canada	L4J 1W3
71	Investigational Site Number 1248004	Toronto		Canada	M3M 3E5
72	Investigational Site Number 1248011	Toronto		Canada	M9W 4L6
73	Investigational Site Number 1248005	Vancouver		Canada	V5Y 3W2
74	Investigational Site Number 1248008	Victoriaville		Canada	G6P 6P6
75	Investigational Site Number 2038007	Brandys		Czechia	250 01
76	Investigational Site Number 2038003	Havirov		Czechia	736 01
77	Investigational Site Number 2038004	Krnov		Czechia	794 01
78	Investigational Site Number 2038011	Ostrava		Czechia	710 00
79	Investigational Site Number 2038006	Pardubice		Czechia	530 02
80	Investigational Site Number 2038010	Plzen		Czechia	363 01
81	Investigational Site Number 2038005	Prague		Czechia	18100
82	Investigational Site Number 2038001	Praha 10 - Uhrineves		Czechia	104 00
83	Investigational Site Number 2038009	Praha 1		Czechia	110 00
84	Investigational Site Number 2038013	Praha 2		Czechia	128 00
85	Investigational Site Number 2038002	Praha 4		Czechia	149 00
86	Investigational Site Number 2038008	Praha 9		Czechia	190 14
87	Investigational Site Number 2508005	Corbeil-Essonnes		France	91106
88	Investigational Site Number 2508006	La Roche Sur Yon		France	85925
89	Investigational Site Number 2508007	La Tronche		France	38700
90	Investigational Site Number 2508003	Mulhouse		France	68100
91	Investigational Site Number 2508002	Nantes Cedex 1		France	44093
92	Investigational Site Number 2508001	Paris		France	75018
93	Investigational Site Number 2508004	Saint-Mandé		France	94160
94	Investigational Site Number 3808010	Catania		Italy	95122
95	Investigational Site Number 3808003	Catania		Italy	95123
96	Investigational Site Number 3808002	Chieti		Italy	66100
97	Investigational Site Number 3808004	Milano		Italy	20122
98	Investigational Site Number 3808005	Milano		Italy	20132
99	Investigational Site Number 3808009	Pavia		Italy	27100
100	Investigational Site Number 3808008	Roma		Italy	00133
101	Investigational Site Number 3808001	Roma		Italy	00168
102	Investigational Site Number 3808007	Roma		Italy	161
103	Investigational Site Number 3808011	San Giovanni Rotondo		Italy	71013
104	Investigational Site Number 3808006	Siena		Italy	53100
105	Investigational Site Number 4288004	Kuldiga		Latvia	3301
106	Investigational Site Number 4288008	Limbazi		Latvia	4000
107	Investigational Site Number 4288003	Ogre		Latvia	5001
108	Investigational Site Number 4288007	Riga		Latvia	LV -1021
109	Investigational Site Number 4288001	Riga		Latvia	LV-1002
110	Investigational Site Number 4288002	Riga		Latvia	LV-1011
111	Investigational Site Number 4288006	Sigulda		Latvia	LV-2150
112	Investigational Site Number 4288005	Talsi		Latvia	LV-3200
113	Investigational Site Number 4848002	Chihuahua		Mexico	31200
114	Investigational Site Number 4848003	Cuernavaca		Mexico	62250
115	Investigational Site Number 4848007	Durango, Durango		Mexico	34080
116	Investigational Site Number 4848011	Mexico City		Mexico	06700
117	Investigational Site Number 4848005	Monterrey		Mexico	07960-6136
118	Investigational Site Number 4848001	Monterrey		Mexico	64020
119	Investigational Site Number 4848012	Monterrey		Mexico	64460
120	Investigational Site Number 6438008	Chelyabinsk		Russian Federation	454047
121	Investigational Site Number 6438006	Dzerzhinsky		Russian Federation	140091
122	Investigational Site Number 6438009	Kemerovo		Russian Federation	650002
123	Investigational Site Number 6438010	Novosibirsk		Russian Federation	630091
124	Investigational Site Number 6438013	Saint-Petersburg		Russian Federation	190013
125	Investigational Site Number 6438003	Saint-Petersburg		Russian Federation	192012
126	Investigational Site Number 6438002	Saint-Petersburg		Russian Federation	194358
127	Investigational Site Number 6438005	Saint-Petersburg		Russian Federation	195213
128	Investigational Site Number 6438001	Saint-Petersburg		Russian Federation	196601
129	Investigational Site Number 6438012	Saratov		Russian Federation	410054
130	Investigational Site Number 6438014	St. Petersburg		Russian Federation	194354
131	Investigational Site Number 6438015	Volgograd		Russian Federation	400001
132	Investigational Site Number 6438007	Vsevolozhsk		Russian Federation	188643
133	Investigational Site Number 6438011	Yaroslavl		Russian Federation	150002
134	Investigational Site Number 7038005	Bardejov		Slovakia	085 01
135	Investigational Site Number 7038009	Bratislava		Slovakia	8210
136	Investigational Site Number 7038001	Kosice		Slovakia	4014
137	Investigational Site Number 7038006	Lucenec		Slovakia	984 01
138	Investigational Site Number 7038008	Nove Zamky		Slovakia	940 01
139	Investigational Site Number 7038004	Povazska Bystrica		Slovakia	1701
140	Investigational Site Number 7038002	Roznava		Slovakia	048 01
141	Investigational Site Number 7038007	Sabinov		Slovakia	08301
142	Investigational Site Number 7038003	Vrutky		Slovakia	038 61
143	Investigational Site Number 7248006	Barcelona		Spain	8035
144	Investigational Site Number 7248002	Córdoba		Spain	14011
145	Investigational Site Number 7248005	Malaga Malaga		Spain	29006
146	Investigational Site Number 7248010	Santa Coloma De Gramenet		Spain	08923
147	Investigational Site Number 7248009	Santiago De Compostela		Spain	15706
148	Investigational Site Number 7248004	Sevilla		Spain	41010
149	Investigational Site Number 7248008	Sevilla		Spain	41013
150	Investigational Site Number 7248001	Sevilla		Spain	41071
151	Investigational Site Number 7248003	Valencia Valencia		Spain	46014
152	Investigational Site Number 7248007	Zaragoza		Spain	50009
153	Investigational Site Number 8268008	Darlington		United Kingdom	DL3 6HX
154	Investigational Site Number 8268004	Dundee		United Kingdom	DD1 9SY
155	Investigational Site Number 8268006	Exeter		United Kingdom	EX2 5DW
156	Investigational Site Number 8268001	Hull		United Kingdom	HU3 2RW
157	Investigational Site Number 8268002	Huntingdon		United Kingdom	PE29 6NT
158	Investigational Site Number 8268007	Sheffield		United Kingdom	S5 7AU
159	Investigational Site Number 8268003	Southampton		United Kingdom	SO30 3JB
160	Investigational Site Number 8268005	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

• Lexicon Pharmaceuticals
• Sanofi

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Apr 12, 2018
• Statistical Analysis Plan - Nov 15, 2019

More Information

Publications

None provided.

• Responsible Party: Lexicon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03351478
• Other Study ID Numbers: EFC14867; 2016-001803-22; U1111-1190-7607
• First Posted: Nov 22, 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; Empagliflozin; (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 160 investigative sites in Bulgaria, Canada, Czechia, France, Italy, Latvia, Mexico, Russian Federation, Slovakia, Spain, United Kingdom, and the United States from 27 November 2017 to 16 May 2019.
Pre-assignment Detail	Participants with a diagnosis of Type 2 Diabetes Mellitus were enrolled in 1 of 3 treatment groups, Sotagliflozin, Empagliflozin, or Placebo. Participants were randomly assigned in the ratio of 2:2:1 to these reporting groups.

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 milligrams (mg) administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
Period Title: Overall Study
STARTED	307	309	154
COMPLETED	293	292	147
NOT COMPLETED	14	17	7

Baseline Characteristics

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo	Total
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.	Total of all reporting groups
Overall Participants	307	309	154	770
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.9 (9.7)	59.7 (9.6)	59.8 (9.6)	59.4 (9.6)
Sex: Female, Male (Count of Participants)
Female	141 45.9%	158 51.1%	75 48.7%	374 48.6%
Male	166 54.1%	151 48.9%	79 51.3%	396 51.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	56 18.2%	66 21.4%	33 21.4%	155 20.1%
Not Hispanic or Latino	251 81.8%	243 78.6%	121 78.6%	615 79.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	18 5.9%	21 6.8%	8 5.2%	47 6.1%
Asian	17 5.5%	11 3.6%	4 2.6%	32 4.2%
Native Hawaiian or Other Pacific Islander	2 0.7%	0 0%	0 0%	2 0.3%
Black or African American	13 4.2%	13 4.2%	5 3.2%	31 4%
White	256 83.4%	257 83.2%	137 89%	650 84.4%
More than one race	0 0%	1 0.3%	0 0%	1 0.1%
Unknown or Not Reported	1 0.3%	6 1.9%	0 0%	7 0.9%
Hemoglobin A1c (HbA1c) (percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of HbA1c]	8.23 (0.84)	8.21 (0.93)	8.21 (0.93)	8.22 (0.90)
Systolic Blood Pressure (SBP) (millimeter of mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeter of mercury (mmHg)]	134.55 (13.56)	131.64 (12.18)	133.19 (12.53)	133.11 (12.87)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c) % at Week 26
Description	An analysis of covariance (ANCOVA) model was used for the analysis.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
Measure Participants	307	309	154
Mean (Standard Error) [percentage of HbA1c]	-0.7 (0.1)	-0.8 (0.1)	-0.3 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Placebo
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and the 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	-0.43
	Confidence Interval	(2-Sided) 95%; -0.62 to -0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Empagliflozin 25 mg
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and the country as fixed effects, and baseline HbA1c as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.145
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants from the ITT population, all randomized participants with data available at the given time point for analysis. Missing data was imputed using washout imputation method.

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
Measure Participants	146	151	84
Least Squares Mean (Standard Error) [mmHg]	-5.6 (1.3)	-6.7 (1.3)	-3.5 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Placebo
	Comments	The change from baseline to Week 12 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤ 8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No) and the country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1529
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-2.05
	Confidence Interval	(2-Sided) 95%; -4.87 to 0.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.43
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Empagliflozin 25 mg
	Comments	The change from baseline to Week 12 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤ 8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No) and the country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3377
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; -1.21 to 3.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.21
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal 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 was imputed using washout imputation method under the missing not at random framework.

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
Measure Participants	307	309	154
Least Squares Mean (Standard Error) [millimole per liter (mmol/L)]	-1.3 (0.2)	-1.2 (0.9)	-0.4 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Placebo
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and the country as fixed effects, and baseline 2-hour postprandial glucose 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	-0.91
	Confidence Interval	(2-Sided) 95%; -1.33 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Empagliflozin 25 mg
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), randomization strata of mean SBP (<130, ≥ 130 mmHg) at screening, and the country as fixed effects, and baseline 2-hour postprandial glucose as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8397
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.17
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) 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 was imputed using the retrieved dropouts imputation method.

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
Measure Participants	307	309	154
Least Squares Mean (Standard Error) [mmol/L]	-1.3 (0.2)	-1.6 (0.2)	-0.5 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Placebo
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and the country as fixed effects, and baseline fasting plasma glucose as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.25 to -0.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.23
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Empagliflozin 25 mg
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and the country as fixed effects, and baseline fasting plasma glucose as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1339
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Body Weight 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 was imputed using the retrieved dropouts imputation method.

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
Measure Participants	307	309	154
Least Squares Mean (Standard Error) [kilogram (kg)]	-2.7 (0.3)	-3.2 (0.3)	-0.5 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Placebo
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and the country as fixed effects, and baseline 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	-2.25
	Confidence Interval	(2-Sided) 95%; -2.95 to -1.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Empagliflozin 25 mg
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and the country as fixed effects, and baseline weight as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1407
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; -0.17 to 1.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Sitting SBP at Week 12 for All Participants
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 was imputed using the retrieved dropouts imputation method.

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
Measure Participants	307	309	154
Least Squares Mean (Standard Error) [mmHg]	-1.7 (0.8)	-2.8 (0.8)	-0.4 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Placebo
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤ 8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No) and the country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0325
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-2.03
	Confidence Interval	(2-Sided) 95%; -3.89 to -0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.95
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Empagliflozin 25 mg
	Comments	The change from baseline to Week 26 is analyzed using an ANCOVA model using multiple imputations to fill in missing data and is parameterized with treatment groups, randomization strata of HbA1c (≤ 8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No) and the country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1565
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -0.42 to 2.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.78
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With HbA1c <6.5% at Week 26
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Missing data at Week 26 were assigned a status of nonresponder in the analysis.

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
Measure Participants	307	309	154
Number [percentage of participants]	12.1 3.9%	11.7 3.8%	3.9 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Placebo
	Comments	The percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (<130, ≥130 mmHg) at the screening.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0048
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	percentage difference
	Estimated Value	8.1
	Confidence Interval	(2-Sided) 95%; 3.36 to 12.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With HbA1c <7.0% at Week 26
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Missing data at Week 26 were assigned a status of nonresponder in the analysis.

Arm/Group Title	Sotagliflozin 400 mg	Empagliflozin 25 mg	Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.	Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
Measure Participants	307	309	154
Number [percentage of participants]	32.6 10.6%	35.6 11.5%	15.6 10.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sotagliflozin 400 mg, Placebo
	Comments	The percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (<130, ≥130 mmHg) at the screening.
	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	16.9
	Confidence Interval	(2-Sided) 95%; 9.26 to 24.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	First dose of study drug to last dose of study drug (up to 26 weeks) + 4 weeks (Approximately 30 weeks)
Adverse Event Reporting Description	Safety population included all randomized participants who received at least one dose of study drug.
Arm/Group Title	Sotagliflozin 400 mg		Empagliflozin 25 mg		Placebo
Arm/Group Description	Following a 2-week run-in period, sotagliflozin 400 mg (milligrams) administered as two 200 mg tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.		Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.		Following a 2-week run-in period, placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.
All Cause Mortality
	Sotagliflozin 400 mg		Empagliflozin 25 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Serious Adverse Events
	Sotagliflozin 400 mg		Empagliflozin 25 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/307 (3.3%)		13/309 (4.2%)		9/154 (5.8%)
Blood and lymphatic system disorders
Abdominal lymphadenopathy	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Cardiac disorders
Atrial flutter	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Sinus node dysfunction	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Right ventricular failure	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Myocardial fibrosis	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Gastrointestinal disorders
Umbilical hernia	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Diverticulum intestinal	0/307 (0%)		2/309 (0.6%)		0/154 (0%)
Intestinal obstruction	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Duodenal ulcer	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Hepatobiliary disorders
Cholecystitis acute	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Gallbladder polyp	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Infections and infestations
Cellulitis	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Erysipelas	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Diverticulitis	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Infection	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Pneumonia	0/307 (0%)		0/309 (0%)		2/154 (1.3%)
Sepsis	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Urosepsis	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Vestibular neuronitis	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Injury, poisoning and procedural complications
Lumbar vertebral fracture	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intraductal proliferative breast lesion	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Adenocarcinoma of colon	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Meningioma	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Laryngeal cancer	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Nasal cavity cancer	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Nervous system disorders
Cerebral haematoma	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Cerebral ischaemia	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Cerebrovascular accident	0/307 (0%)		2/309 (0.6%)		0/154 (0%)
Ischaemic stroke	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Presyncope	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Pulmonary embolism	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Pulmonary infarction	0/307 (0%)		1/309 (0.3%)		0/154 (0%)
Pulmonary mass	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Vascular disorders
Hypotension	1/307 (0.3%)		0/309 (0%)		0/154 (0%)
Hypertensive crisis	0/307 (0%)		0/309 (0%)		1/154 (0.6%)
Other (Not Including Serious) Adverse Events
	Sotagliflozin 400 mg		Empagliflozin 25 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/307 (18.9%)		68/309 (22%)		39/154 (25.3%)
Gastrointestinal disorders
Constipation	3/307 (1%)		5/309 (1.6%)		6/154 (3.9%)
Diarrhoea	10/307 (3.3%)		8/309 (2.6%)		5/154 (3.2%)
Infections and infestations
Genital infection fungal	7/307 (2.3%)		5/309 (1.6%)		0/154 (0%)
Influenza	5/307 (1.6%)		9/309 (2.9%)		5/154 (3.2%)
Nasopharyngitis	12/307 (3.9%)		20/309 (6.5%)		5/154 (3.2%)
Urinary tract infection	11/307 (3.6%)		8/309 (2.6%)		2/154 (1.3%)
Vulvovaginal mycotic infection	5/307 (1.6%)		10/309 (3.2%)		1/154 (0.6%)
Metabolism and nutrition disorders
Hyperglycaemia	6/307 (2%)		6/309 (1.9%)		9/154 (5.8%)
Any Hypoglycaemia	2/307 (0.7%)		9/309 (2.9%)		7/154 (4.5%)
Documented Symptomatic Hypoglycaemia	1/307 (0.3%)		8/309 (2.6%)		3/154 (1.9%)
Musculoskeletal and connective tissue disorders
Back pain	6/307 (2%)		3/309 (1%)		4/154 (2.6%)
Nervous system disorders
Headache	7/307 (2.3%)		8/309 (2.6%)		6/154 (3.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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.