Efficacy and Safety of Sotagliflozin Versus Placebo in Pa... | NCT03285594

NCT03285594

ID	Type	Description	Link
2016-001804-43	EudraCT Number
U1111-1190-7567	Other Identifier	UTN

Status Module

Name	Class
Sanofi	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Following a 4-week run-in period, participants were randomized to matching placebo to sotagliflozin 200 milligrams (mg) administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Drug: Insulin glargine (HOE901) Drug: Placebo Drug: Oral Antidiabetes Drugs (OADs)
Sotagliflozin 200 mg	Experimental	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Drug: Sotagliflozin Drug: Insulin glargine (HOE901) Drug: Placebo Drug: Oral Antidiabetes Drugs (OADs)
Sotagliflozin 400 mg	Experimental	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Drug: Sotagliflozin Drug: Insulin glargine (HOE901) Drug: Oral Antidiabetes Drugs (OADs)

Name	Type	Description	Arm Group Labels	Other Names
Sotagliflozin	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 (HbA1c) at Week 18	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline and Week 18

Secondary Outcomes

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

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 Mellitus (T2DM) using any types of basal insulin alone or in combination with up to 2 OADs.
Participants have given written informed consent to participate in the study in accordance with local regulations.

Exclusion criteria:

At the time of Screening age <18 years or <legal age of majority, whichever is greater.
Type 1 diabetes mellitus.
Oral antidiabetic drugs dose not stable for 8 weeks before Screening.
Use of basal insulin therapy (e.g., insulin glargine, Neutral Protamine Hagedorn (NPH), detemir, or degludec) for less than 6 months before Screening.
Dose of basal insulin (e.g., insulin glargine, NPH, detemir, or degludec) not stable for 8 weeks before Screening (i.e., total daily insulin dose increased or decreased by more than 20%).
Known unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema that is likely to require laser, surgical treatment during study period.
Use of injectable diabetes drugs other than basal insulin (e.g., insulin glargine, NPH, detemir, or degludec), i.e., prandial or rapid-acting insulins, short-acting insulins, glucagon-like peptide 1 (GLP-1) receptor agonists, or inhaled prandial insulin (Afrezza) within 8 weeks of Screening.
Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the trial.
Use of systemic glucocorticoids (excluding topical, intra articular, or ophthalmic application, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease that, according to the Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.
Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization.
Known presence of factors that interfere with the Central Lab HbA1c measurement (e.g., genetic hemoglobin (Hb) variants) compromising the reliability of HbA1c assessment or medical conditions that affect interpretation of HbA1c results (e.g., blood transfusion or severe blood loss in the last 3 months prior to randomization, any condition that shortens erythrocyte survival).
Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from prior to Screening, whichever is longer.
Participants unwilling to perform self-monitoring of blood glucose (SMBG), complete the patient diary, or comply with study visits and other study procedures as required per protocol.
HbA1c <7.5% or HbA1c >10.5% measured by the central laboratory at Screening.
HbA1c <7% measured by the central laboratory at Visit 5 (Week -1).
History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.
Women of childbearing potential not willing to use highly effective method(s) of birth control during the study treatment period and the follow-up period, or who are unwilling or unable to be tested for pregnancy during the study.
Mean of 3 separate blood pressure measurements >180 mmHg (systolic blood pressure [SBP]) or >100 mmHg (diastolic blood pressure [DBP]).
History of gastric surgery including history of gastric banding or inflammatory bowel disease within 3 years prior to the Screening Visit.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of the normal laboratory range
Total bilirubin >1.5 times the upper limit of the normal laboratory range (except in case of Gilbert's syndrome).

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

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

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 8406028		Mesa	Arizona	85213-5226	United States
Investigational Site Number 8406013

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without oral antidiabetes drugs [OADs]) continued throughout the study.

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	Mar 12, 2018	Apr 12, 2021

Arm/Group Information

ID	Title	Description
BG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
BG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
BG002	Sotagliflozin 400 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
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
	BG00062.2± 8.9 BG00162.1± 10.2 BG00262.7± 9.1 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00058 BG00165 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00012 BG00125 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0002 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Bulgaria

Title	Measurements
	BG0009 BG00113 BG002

Hemoglobin A1c (HbA1c)

Mean

Standard Deviation

percentage of HbA1c

Title

Denominators

Categories

Title	Measurements
	BG0008.76± 0.79 BG0018.76± 0.83 BG002

Systolic Blood Pressure (SBP)

Mean

Standard Deviation

millimeter of Mercury (mmHg)

Title

Denominators

Categories

Title	Measurements
	BG000137.59± 14.12 BG001136.40± 15.54 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 18

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

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

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline and Week 18

ID	Title	Description
OG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG002	Sotagliflozin 400 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.

Units	Counts
Participants	OG000144 OG001141 OG002286

Title

Denominators

Categories

Title	Measurements
	OG000-0.27± 0.073 OG001-0.72± 0.073 OG002-0.81± 0.056

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 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at Week -1, randomization strata of mean SBP (<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline HbA1c as a covariate.	ANCOVA		<0.0001		Difference in Least Square (LS) Means	-0.45	Standard Error of the Mean	0.094	2-Sided	95	-0.638	-0.271					Superiority

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18

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

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

Posted

Least Squares Mean

Standard Error

milligram per deciliter (mg/dL)

Baseline and Week 18

ID	Title	Description
OG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG002

Secondary

Change From Baseline in Body Weight at Week 18

An ANCOVA model was used for the analysis.

Posted

Least Squares Mean

Standard Error

kilogram (kg)

Baseline and Week 18

ID	Title	Description
OG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG002	Sotagliflozin 400 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.

Secondary

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

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

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

Posted

Least Squares Mean

Standard Error

mmHg

Baseline and Week 12

ID	Title	Description
OG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.

Secondary

Change From Baseline in SBP at Week 12 for All Participants

An ANCOVA model was used for the analysis.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG002	Sotagliflozin 400 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.

Secondary

Change From Baseline in HbA1c at Week 52

An ANCOVA model was used for the analysis.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline and Week 52

ID	Title	Description
OG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG002	Sotagliflozin 400 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.

Secondary

Change From Baseline in Body Weight at Week 52

An ANCOVA model was used for the analysis.

Posted

Least Squares Mean

Standard Error

Baseline and Week 52

ID	Title	Description
OG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG002	Sotagliflozin 400 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.

Secondary

Percentage of Participants With Adverse Events (AEs)

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

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

First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 weeks

ID	Title	Description
OG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
OG002

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 randomised 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 55.7 weeks

ID	Title	Description
OG000	Placebo	Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without oral antidiabetes drugs [OADs]) continued throughout the study.
OG001	Sotagliflozin 200 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 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	2	144	16	144	30	144
EG001	Sotagliflozin 200 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	1	141	19	141	18	141
EG002	Sotagliflozin 400 mg	Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	6	285	28	285	45	285

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Aortic stenosis	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Hypertension	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Adenocarcinoma pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Death	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Non-cardiac chest pain	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Sudden cardiac death	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Jaw fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Multiple injuries	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Postoperative thrombosis	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Tendon injury	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Alanine aminotransferase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected144 at risk EG0010 affected141 at risk EG0022 affected285 at risk
Angina unstable	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Atrial flutter	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Cardiac arrest	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Cardiac failure	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Cardiogenic shock	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Coronary artery disease	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0022 affected285 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Left ventricular failure	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Myocardial infarction	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Reperfusion arrhythmia	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Cervicobrachial syndrome	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Syncope	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0011 affected141 at risk EG0021 affected285 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Retinal artery thrombosis	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Retinopathy proliferative	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Renal haematoma	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Urethral stenosis	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Biliary dyskinesia	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0012 affected141 at risk EG0020 affected285 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Gastroenteritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Infected bite	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Localised infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Osteomyelitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Osteomyelitis acute	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Postoperative wound infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Pyelonephritis chronic	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0010 affected141 at risk EG0021 affected285 at risk
Renal abscess	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Scrotal abscess	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 at risk
Enlarged uvula	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected144 at risk EG0010 affected141 at risk EG0020 affected285 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected144 at risk EG0011 affected141 at risk EG0020 affected285 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
D000069036	Insulin Glargine

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0009 affected144 at risk EG0014 affected141 at risk EG00210 affected285 at risk
Nasopharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0007 affected144 at risk EG0019 affected141 at risk EG00214 affected285 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0008 affected144 at risk EG0011 affected141 at risk EG00214 affected285 at risk
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0008 affected144 at risk EG0016 affected141 at risk EG00211 affected285 at risk