Efficacy and Safety of Sotagliflozin Versus Placebo in Pa... | NCT03066830

NCT03066830

ID	Type	Description	Link
2016-002826-35	EudraCT Number
U1111-1186-2612	Other Identifier	UTN

Status Module

Sponsor/Collaborators Module

Name	Class
Sanofi	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sotagliflozin 400 mg	Experimental	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Drug: Sotagliflozin (SAR439954)
Placebo	Placebo Comparator	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Drug: Placebo Drug: Metformin Drug: Sulfonylurea

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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26	Missing data are imputed using the retrieved dropouts imputation method. An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline to Week 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.	Baseline to Week 26
Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg

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]. Participants may be reported in more than one category.

Eligibility Module

Eligibility Criteria

Inclusion criteria :

Participants with T2D treated with a Sulfonylurea (≥half the maximum recommended dose as per local label or maximum tolerated dose [documented]) as monotherapy or in combination with Metformin (≥1500 mg per day or maximum tolerated dose [documented]) each at a stable dose for at least 12 weeks without a dose adjustment before screening.
Signed written informed consent.

Exclusion criteria:

At the time of screening, age <18 years or < legal age of majority, whichever is greater.
Body Mass Index (BMI) ≤20 or >45 kilograms per meter square (kg/m^2) at Screening.
Hemoglobin A1c (HbA1c) <7% or HbA1c >10% via central lab test at screening.
Fasting plasma glucose (FPG) >15 mmol/L (270 mg/dL) measured by the central laboratory at screening (Visit 1), and confirmed (>15 mmol/L [270 mg/dL]) by a repeat test before randomization.
Women of childbearing potential with no effective contraceptive method.
Treated with an antidiabetic pharmacological regimen other than a Sulfonylurea at a stable dose with or without Metformin within 12 weeks preceding the screening visit.
Previous insulin use >1 month (at any time, aside from treatment of gestational diabetes).
History of prior gastric surgical procedure including gastric banding or inflammatory bowel disease within 3 years before the Screening Visit.
History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
History of severe hypoglycemia within 6 months prior to the Screening visit.
Systolic blood pressure (SBP) >180 millimeter per mercury (mmHg) or diastolic blood pressure (DBP) >100 mmHg or history of hypertensive emergency.
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).
Use of systemic glucocorticoids (excluding topical or ophthalmic, application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
Pregnancy, breastfeeding.
Participants is unwilling to perform self-monitoring of blood glucose (SMBG), and complete the participant's diary as required per protocol.

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

Contacts/Locations Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 8403003		Litchfield Park	Arizona	85340	United States
Investigational Site Number 8403018

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 21, 2017	Apr 12, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Intent-to-treat (ITT) population included all randomized participants.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
BG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
BG002	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
	BG00063.0± 9.9 BG00163.3± 8.8 BG00263.1± 9.3

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000124 BG001104 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00043 BG00153 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Hemoglobin A1c (HbA1c)

Mean

Standard Deviation

percentage of HbA1c

Title

Denominators

Categories

Title	Measurements
	BG0008.18± 0.83 BG0018.20± 0.83 BG002

Systolic Blood Pressure (SBP)

Mean

Standard Deviation

millimeter of mercury (mmHg)

Title

Denominators

Categories

Title	Measurements
	BG000133.08± 14.21 BG001134.30± 13.01 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

Missing data are imputed using the retrieved dropouts imputation method. An analysis of covariance (ANCOVA) model was used for the analysis.

Intent-to-treat (ITT) population included all randomized participants.

Posted

Least Squares Mean

Standard Error

percentage HbA1c

Baseline to Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Units	Counts
Participants	OG000254 OG001253

Title

Denominators

Categories

Title	Measurements
	OG0000.06± 0.082 OG001-0.70± 0.068

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 OG001	The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of Metformin use at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.	ANCOVA		< 0.0001		Difference in Least Square (LS) Mean	-0.76	Standard Error of the Mean	0.095	2-Sided	95	-0.946	-0.574					Superiority

Secondary

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

Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.

ITT population included all randomized participants.

Posted

Least Squares Mean

Standard Error

millimole per liter (mmol/L)

Baseline to Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Units	Counts

Secondary

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

Missing data are imputed using the washout imputation method under the missing, not at random framework. An ANCOVA model was used for the analysis.

Analysis was performed on ITT population in participants with baseline SBP ≥130 mmHg.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Secondary

Change From Baseline in SBP at Week 12 for All Participants

Missing data are imputed using washout imputation method under the missing not at random framework. An ANCOVA model was used for the analysis.

ITT population included all randomized participants .

Posted

Least Squares Mean

Standard Deviation

mmHg

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Units	Counts

Secondary

Change From Baseline in Body Weight at Week 26

Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.

ITT population included all randomized participants.

Posted

Least Squares Mean

Standard Deviation

kilogram (kg)

Baseline to Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Units	Counts

Secondary

Percentage of Participants With HbA1c <6.5% at Week 26

ITT population included all randomized participants.

Posted

Number

percentage of participants

Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Units	Counts
Participants

Secondary

Percentage of Participants With HbA1c <7.0% at Week 26

ITT population included all randomized participants.

Posted

Number

percentage of participants

Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Units	Counts
Participants

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]. Participants may be reported in more than one category.

Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product.

Posted

Number

percentage of participants

Up to 79 weeks in the treatment period

ID	Title	Description
OG000	Placebo	Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
OG001	Sotagliflozin 400 mg

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, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks. One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study is included in the Sotagliflozin 400 mg arm in the safety population.	2	253	40	253	90	253
EG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 milligrams (mg), orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks. One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study is included in the Sotagliflozin 400 mg arm in the safety population.	2	254	32	254	71	254

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0002 affected253 at risk EG0010 affected254 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Pituitary tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Prostate cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Rectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Non-cardiac chest pain	General disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Pyrexia	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Sudden cardiac death	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Endometrial hyperplasia	Reproductive system and breast disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Uterine prolapse	Reproductive system and breast disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Anastomotic ulcer	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0011 affected254 at risk
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0011 affected254 at risk
Acute left ventricular failure	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0012 affected254 at risk
Angina pectoris	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0012 affected254 at risk
Angina unstable	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0011 affected254 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Cardiac failure	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Coronary artery disease	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0003 affected253 at risk EG0011 affected254 at risk
Coronary artery occlusion	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Nodal arrhythmia	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Silent myocardial infarction	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0002 affected253 at risk EG0010 affected254 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0002 affected253 at risk EG0010 affected254 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0012 affected254 at risk
Nerve compression	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Post stroke epilepsy	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Sciatica	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Syncope	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Cataract	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Glaucoma	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Retinal detachment	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Visual impairment	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Vitreous haemorrhage	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Femoral hernia	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0003 affected253 at risk EG0011 affected254 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0011 affected254 at risk
Diverticulitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Gangrene	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Pneumonia	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0011 affected254 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 affected253 at risk EG0010 affected254 at risk
Septic shock	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected253 at risk EG0011 affected254 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG00011 affected253 at risk EG00122 affected254 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG00048 affected253 at risk EG00114 affected254 at risk
Nasopharyngitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG00023 affected253 at risk EG00121 affected254 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG00019 affected253 at risk EG0019 affected254 at risk
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0008 affected253 at risk EG00119 affected254 at risk

ID	Term
D003924	Diabetes Mellitus, Type 2

ID	Term
C575681	(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
D008687	Metformin
D013453	Sulfonylurea Compounds

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
D014508	Urea
D000577	Amides
D013450	Sulfones
D013457	Sulfur Compounds