Efficacy and Safety of Sotagliflozin Versus Glimepiride a... | NCT03332771

ID	Type	Description	Link
2016-001801-17	EudraCT Number
U1111-1190-7596	Other Identifier	UTN

Status Module

Name	Class
Sanofi	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

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

Name	Type	Description	Arm Group Labels	Other Names
Sotagliflozin (SAR439954)	Drug	Pharmaceutical form: tablet Route of administration: oral	Sotagliflozin 200 mg Sotagliflozin 400 mg

Outcomes Module

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

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hemoglobin A1c at Week 26	An ANCOVA model was used for the analysis.	Baseline, Week 26
Change From Baseline in Body Weight at Week 26 and 52	An ANCOVA model was used for the analysis.

Other Outcomes

Measure	Description	Time Frame
Percentage of Participants With Hypoglycemic Events	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 Module

Eligibility Criteria

Inclusion criteria :

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

Exclusion criteria:

Age <18 years at the Screening Visit or <legal age of majority, whichever is greater.
Type 1 diabetes mellitus.
HbA1c, HbA1c <7.0% or HbA1c >10% at Screening.
Fasting Plasma Glucose (FPG) >15 millimoles per liter (mmol/L) (>270 milligram per deciliter [mg/dL]) measured by the central laboratory at Screening (Visit 1) and confirmed by a repeat test (>15 mmol/L [>270 mg/dL]) before randomization.
Body mass index ≤20 or >45 kilogram per meter square (kg/m^2) at Screening.
Pregnant (confirmed by pregnancy test at the Screening) or breast-feeding women.
Women of childbearing potential (WOCBP) not willing to use highly effective method(s) of birth control during the study treatment period and the follow-up period, or who are unwilling or unable to be tested for pregnancy (see Appendix A) during the study.
Previous use of any antidiabetic drug other than Metformin within 12 weeks preceding the Screening Visit.
Use of a selective Sodium-glucose co-transporter-2 (SGLT2) inhibitor (e.g., Canagliflozin, Dapagliflozin, or Empagliflozin) within 3 months prior to the Screening visit.
Use of systemic glucocorticoids (excluding topical, or ophthalmic application, intra-articular, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
Previous insulin use >1 month (at any time, except for treatment of gestational diabetes).
History of prior gastric surgical procedure, including gastric banding, or inflammatory bowel disease within 3 years prior to the Screening Visit.
Difficulty swallowing such that the participants cannot take the investigational medicinal product (IMP).
History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
Mean of 3 separate blood pressure measurements >180 millimeter of mercury (mmHg) (SBP) or >100 mmHg (DBP).
History of hypertensive emergency within 12 weeks prior to Screening.
Participants who have previously been randomized in any clinical trial of Sotagliflozin/LX4211.
Participants with severe renal disease as defined by an estimated glomerular filtration rate (eGFR) of <30 milliliter per minute per meter square (mL/min/1.73 m^2) at Screening, based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation (or according to the renal function restrictions of metformin use defined in the local approved label).
Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease that, according to Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.
Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range (ULN).
Total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome).
Participants who have taken other investigational drugs within 12 weeks or 5 half-lives from Screening whichever is longer.
Participants unwilling or unable to perform self-monitoring blood glucose (SMBG), complete the participant diary, or comply with study visits and other study procedures as required per protocol.
Participants with contraindication to glimepiride as per local labelling.
Participants with contraindication to metformin as per local labelling.

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

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

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 8407040		Birmingham	Alabama	35205	United States
Investigational Site Number 8407048

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
FG001	Sotagliflozin 400 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 11, 2018	Apr 12, 2021

Arm/Group Information

ID	Title	Description
BG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
BG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
BG002	Sotagliflozin 200 mg	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
BG003	Glimepiride	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
BG004	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
	BG00058.8± 11.2 BG00159.7± 10.4 BG00258.6± 9.9 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00077 BG001157 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00048 BG00185 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Bulgaria

Title	Measurements
	BG0007 BG00117 BG002

Hemoglobin A1c (HbA1c)

Mean

Standard Deviation

percentage of HbA1c

Title

Denominators

Categories

Title	Measurements
	BG0008.12± 0.73 BG0018.09± 0.78 BG002

Systolic Blood Pressure (SBP)

Mean

Standard Deviation

millimeter of mercury (mmHg)

Title

Denominators

Categories

Title	Measurements
	BG000133.23± 14.90 BG001133.17± 14.37 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 at Week 52

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

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

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline, Week 52

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG002	Sotagliflozin 200 mg	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG003	Glimepiride	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Units	Counts
Participants	OG000159 OG001317 OG002160 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.40± 0.187 OG001-0.65± 0.101 OG002-0.49± 0.114 OG003

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
OG001 OG003	The change from baseline to Week 52 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.	ANCOVA		0.3306		Difference in Least Squares (LS) Mean	0.12	Standard Error of the Mean	0.122	2-Sided	95	-0.120	0.357					Non-Inferiority	The non-inferiority hypothesis was declared significant if the upper bound of the 2-sided 95% confidence interval (CI) for the adjusted mean difference is <0.3.

Secondary

Change From Baseline in Hemoglobin A1c at Week 26

An ANCOVA model was used for the analysis.

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

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline, Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG002	Sotagliflozin 200 mg	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Secondary

Change From Baseline in Body Weight at Week 26 and 52

An ANCOVA model was used for the analysis.

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

Posted

Least Squares Mean

Standard Error

kilogram (kg)

Baseline, Week 26, Week 52

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG002	Sotagliflozin 200 mg	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Secondary

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

An ANCOVA model was used for the analysis.

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

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG002	Sotagliflozin 200 mg	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Secondary

Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12

An ANCOVA model was used for the analysis.

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

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG002	Sotagliflozin 200 mg	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Secondary

Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event

Documented symptomatic hypoglycemia includes the typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L).

ITT population included all randomized participants.

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG002	Sotagliflozin 200 mg	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Secondary

Percentage of Participants With Adverse Events (AEs)

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

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

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG002	Sotagliflozin 200 mg	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Other Pre-specified

Percentage of Participants With Hypoglycemic Events

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].

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).

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

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	Placebo	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	2	159	11	159	30	159
EG001	Sotagliflozin 400 mg	Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	1	317	17	317	49	317
EG002	Sotagliflozin 200 mg	Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	0	159	11	159	21	159
EG003	Glimepiride	Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.	2	317	14	317	22	317

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute left ventricular failure	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG0030 affected317 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Retinal haemorrhage	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Diverticulum intestinal haemorrhagic	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Umbilical hernia	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Death	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Incarcerated hernia	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Influenza like illness	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Sudden cardiac death	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Cholecystitis infective	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Epididymitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Erysipelas	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Pneumonia	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Pneumonia legionella	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Pyelonephritis chronic	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Sepsis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0021 affected159 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Concussion	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Fibula fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0021 affected159 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Vascular graft stenosis	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Vertebral osteophyte	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Oesophageal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Cerebellar stroke	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Hemiparesis	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Syncope	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Alcohol withdrawal syndrome	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Depression	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Adnexa uteri mass	Reproductive system and breast disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0011 affected317 at risk EG0020 affected159 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Hypertension	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected159 at risk EG0010 affected317 at risk EG0020 affected159 at risk EG003
Vasculitis	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected159 at risk EG0010 affected317 at risk EG0021 affected159 at risk EG003

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

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG00011 affected159 at risk EG00114 affected317 at risk EG0028 affected159 at risk EG0037 affected317 at risk
Vulvovaginal mycotic infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0002 affected159 at risk EG00119 affected317 at risk EG0026 affected159 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0008 affected159 at risk EG0015 affected317 at risk EG0022 affected159 at risk EG003
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG00011 affected159 at risk EG00114 affected317 at risk EG0027 affected159 at risk EG003

ID	Term
C575681	(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
C057619	glimepiride
D008687	Metformin