Efficacy and Safety of Sotagliflozin Versus Placebo and E... | NCT03351478

NCT03351478

ID	Type	Description	Link
2016-001803-22	EudraCT Number
U1111-1190-7607	Other Identifier	UTN

Status Module

Name	Class
Sanofi	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sotagliflozin 400 mg	Experimental	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 Drug: Placebo
Empagliflozin 25 mg	Active Comparator	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 Drug: Placebo
Placebo	Placebo Comparator	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

Name	Type	Description	Arm Group Labels	Other Names
Sotagliflozin	Drug	Sotagliflozin 400 mg was administered as two tablets, once daily before the first meal of the day.	Sotagliflozin 400 mg

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

Measure	Description	Time Frame
Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥ 130 mmHg	An ANCOVA model was used for the analysis.	Baseline, Week 12
Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Suman Wason	Lexicon Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 8408035		Birmingham	Alabama	35205	United States
Investigational Site Number 8408028

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sotagliflozin 400 mg	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.
FG001	Empagliflozin 25 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 12, 2018	Apr 12, 2021

Arm/Group Information

ID	Title	Description
BG000	Sotagliflozin 400 mg	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.
BG001	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.
BG002	Placebo	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.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00058.9± 9.7 BG00159.7± 9.6 BG00259.8± 9.6 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000141 BG001158 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00056 BG00166 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG00018 BG00121 BG002

Hemoglobin A1c (HbA1c)

Mean

Standard Deviation

percentage of HbA1c

Title

Denominators

Categories

Title	Measurements
	BG0008.23± 0.84 BG0018.21± 0.93 BG002

Systolic Blood Pressure (SBP)

Mean

Standard Deviation

millimeter of mercury (mmHg)

Title

Denominators

Categories

Title	Measurements
	BG000134.55± 13.56 BG001131.64± 12.18 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Hemoglobin A1c (HbA1c) % at Week 26

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

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

Posted

Mean

Standard Error

percentage of HbA1c

Baseline, Week 26

ID	Title	Description
OG000	Sotagliflozin 400 mg	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.
OG001	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.
OG002	Placebo	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.

Units	Counts
Participants	OG000307 OG001309 OG002154

Title

Denominators

Categories

Title	Measurements
	OG000-0.7± 0.1 OG001-0.8± 0.1 OG002-0.3± 0.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	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.	ANCOVA		< 0.0001		Difference in Least Square (LS) Means	-0.43	Standard Error of the Mean	0.09	2-Sided	95	-0.62	-0.25					Superiority

Secondary

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥ 130 mmHg

An ANCOVA model was used for the analysis.

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.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, Week 12

ID	Title	Description
OG000	Sotagliflozin 400 mg	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.
OG001	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.
OG002	Placebo	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.

Secondary

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

An ANCOVA model was used for the analysis.

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

Posted

Least Squares Mean

Standard Error

millimole per liter (mmol/L)

Baseline, Week 26

ID	Title	Description
OG000	Sotagliflozin 400 mg	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.
OG001	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.
OG002	Placebo	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.

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

An ANCOVA model was used for the analysis.

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

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Sotagliflozin 400 mg	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.
OG001	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.
OG002	Placebo	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.

Secondary

Change From Baseline in Body Weight at Week 26

An ANCOVA model was used for the analysis.

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

Posted

Least Squares Mean

Standard Error

kilogram (kg)

Baseline, Week 26

ID	Title	Description
OG000	Sotagliflozin 400 mg	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.
OG001	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.
OG002	Placebo	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.

Secondary

Change From Baseline in Sitting SBP at Week 12 for All Participants

An ANCOVA model was used for the analysis.

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

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, Week 12

ID	Title	Description
OG000	Sotagliflozin 400 mg	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.
OG001	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.
OG002	Placebo	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.

Secondary

Percentage of Participants With HbA1c <6.5% at Week 26

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

Posted

Number

percentage of participants

Week 26

ID	Title	Description
OG000	Sotagliflozin 400 mg	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.
OG001	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.
OG002	Placebo	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.

Secondary

Percentage of Participants With HbA1c <7.0% at Week 26

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

Posted

Number

percentage of participants

Week 26

ID	Title	Description
OG000	Sotagliflozin 400 mg	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.
OG001	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.
OG002	Placebo	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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 empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.	0	307	10	307	58	307
EG001	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.	1	309	13	309	68	309
EG002	Placebo	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.	0	154	9	154	39	154

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Lumbar vertebral fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Hypertensive crisis	Vascular disorders	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk
Atrial flutter	Cardiac disorders	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Sinus node dysfunction	Cardiac disorders	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Right ventricular failure	Cardiac disorders	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk
Myocardial fibrosis	Cardiac disorders	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Intraductal proliferative breast lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Laryngeal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Nasal cavity cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Pulmonary infarction	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk
Abdominal lymphadenopathy	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Cerebral haematoma	Nervous system disorders	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Cerebral ischaemia	Nervous system disorders	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk
Cerebrovascular accident	Nervous system disorders	Systematic Assessment	EG0000 affected307 at risk EG0012 affected309 at risk EG0020 affected154 at risk
Ischaemic stroke	Nervous system disorders	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk
Presyncope	Nervous system disorders	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Umbilical hernia	Gastrointestinal disorders	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Diverticulum intestinal	Gastrointestinal disorders	Systematic Assessment	EG0000 affected307 at risk EG0012 affected309 at risk EG0020 affected154 at risk
Intestinal obstruction	Gastrointestinal disorders	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk
Duodenal ulcer	Gastrointestinal disorders	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk
Cholecystitis acute	Hepatobiliary disorders	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Gallbladder polyp	Hepatobiliary disorders	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk
Cellulitis	Infections and infestations	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Erysipelas	Infections and infestations	Systematic Assessment	EG0001 affected307 at risk EG0010 affected309 at risk EG0020 affected154 at risk
Diverticulitis	Infections and infestations	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Infection	Infections and infestations	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0022 affected154 at risk
Sepsis	Infections and infestations	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Urosepsis	Infections and infestations	Systematic Assessment	EG0000 affected307 at risk EG0011 affected309 at risk EG0020 affected154 at risk
Vestibular neuronitis	Infections and infestations	Systematic Assessment	EG0000 affected307 at risk EG0010 affected309 at risk EG0021 affected154 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Headache	Nervous system disorders	Systematic Assessment	EG0007 affected307 at risk EG0018 affected309 at risk EG0026 affected154 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0003 affected307 at risk EG0015 affected309 at risk EG0026 affected154 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG00010 affected307 at risk EG0018 affected309 at risk EG0025 affected154 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0006 affected307 at risk EG0013 affected309 at risk EG0024 affected154 at risk
Hyperglycaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0006 affected307 at risk EG0016 affected309 at risk EG0029 affected154 at risk
Any Hypoglycaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected307 at risk EG0019 affected309 at risk EG0027 affected154 at risk
Documented Symptomatic Hypoglycaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected307 at risk EG0018 affected309 at risk EG0023 affected154 at risk
Genital infection fungal	Infections and infestations	Systematic Assessment	EG0007 affected307 at risk EG0015 affected309 at risk EG0020 affected154 at risk
Influenza	Infections and infestations	Systematic Assessment	EG0005 affected307 at risk EG0019 affected309 at risk EG0025 affected154 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG00012 affected307 at risk EG00120 affected309 at risk EG0025 affected154 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG00011 affected307 at risk EG0018 affected309 at risk EG0022 affected154 at risk
Vulvovaginal mycotic infection	Infections and infestations	Systematic Assessment	EG0005 affected307 at risk EG00110 affected309 at risk EG0021 affected154 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
C575681	(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
C570240	empagliflozin