Efficacy and Safety of Semaglutide Once-weekly Versus Pla... | NCT02305381

ID	Type	Description
2013-004502-26	EudraCT Number
U1111-1149-3738	Other Identifier	WHO
JapicCTI-142729	Other Identifier	JAPIC

Status Module

Oversight Module

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Semaglutide 0.5 mg/Week	Experimental	Drug: semaglutide
Semaglutide 1.0 mg/Week	Experimental	Drug: semaglutide
Semaglutide Placebo 0.5 mg/Week	Placebo Comparator	Drug: placebo
Semaglutide Placebo 1.0 mg/Week	Placebo Comparator	Drug: placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
semaglutide	Drug	Injected subcutaneously (s.c. under the skin) once-weekly. As add-on to the pre-trial background medication.	Semaglutide 0.5 mg/Week Semaglutide 1.0 mg/Week

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in HbA1c (Glycosylated Haemoglobin)	Estimated mean change from baseline in HbA1c at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.	Week 0, week 30

Secondary Outcomes

Measure	Description	Time Frame
Change in Body Weight	Estimated mean change from baseline in body weight at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

Eligibility Module

Eligibility Criteria

Inclusion Criteria: - Male or female, age at least 18 years at the time of signing inform consent. For Japan: Male or female, age at least 20 years at the time of signing informed consent - Subjects diagnosed with T2DM (type 2 diabetes mellitus) and on stable diabetes treatment (plus/minus 20 percent change in total daily dose) with basal insulin (minimum of 0.25 IU/kg/day and/or 20 IU/day of: insulin glargine, insulin detemir, insulin degludec and/or NPH insulin) alone or in combination with metformin (minimum of 1500 mg/day or maximal tolerable dose) for 90 days prior to screening - HbA1c (glycosylated haemoglobin) 7.0 - 10.0 percent (53 - 86 mmol/mol) both inclusive Exclusion Criteria: - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method throughout the trial including the 5 weeks follow-up period (adequate contraceptive measures as required by local regulation or practice). Germany: Only highly effective methods of birth control are accepted (ie one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine device), or sexual abstinence or vasectomised partner. Japan: Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives - Treatment with any glucose lowering agents other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (7 days or less in total) with bolus insulin in connection with intercurrent illness - Experienced more than 3 episodes of severe hypoglycaemia within 6 months prior to screening, and/or hypoglycaemia unawareness - History of pancreatitis (acute or chronic) - Screening calcitonin value above or equal to 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome 2 (MEN 2) - Severe renal impairment defined as eGFR (estimated glomerular filtration rate) below 30 mL/min/1.73 m^2 per Modification of Diet in Renal Disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association (NYHA) Class IV

Name	Affiliation	Role
Global Clinical Registry (GCR, 1452)	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novo Nordisk Investigational Site		Phoenix	Arizona	85018	United States
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation
30865526	Background	Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA1C >/=1.0% AND WEIGHT >/=5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13.
	Result	Rodbard H, Lingvay I, Reed J, de la Rosa R, Rose L, Sugimoto D, Araki E, Chu P-L, Wijayasinghe N, Norwood P. Efficacy and safety of semaglutide once-weekly vs placebo as add-on to basal insulin alone or in combination with metformin in subjects with type 2 diabetes (SUSTAIN 5). Diabetologia. 2016; 59: S364-5.
29688502

Label	URL
Clinical Trials at Novo Nordisk	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg subcutaneous (sc) injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
BG001	Semaglutide 1.0 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly for next 4 weeks and then semaglutide 1.0 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
BG002	Placebo	Subjects received placebo (matched to semaglutide) sc injection once weekly for 30 weeks. Placebo injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
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
	ParticipantsBG000132 ParticipantsBG001131 ParticipantsBG002133 ParticipantsBG003

Age, Customized

Number

participants

Title	Denominators	Categories
Adults (18-64 years)	ParticipantsBG000132 ParticipantsBG001131 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000132 ParticipantsBG001131 ParticipantsBG002

Glycosylated haemoglobin

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title	Denominators	Categories
	ParticipantsBG000132 ParticipantsBG001131 ParticipantsBG002

Body weight

Mean

Standard Deviation

Title	Denominators	Categories
	ParticipantsBG000132 ParticipantsBG001131 ParticipantsBG002

Fasting plasma glucose

Mean

Standard Deviation

mg/dL

Title	Denominators	Categories
	ParticipantsBG000132 ParticipantsBG001131 ParticipantsBG002

Insulin dose

Number of participants analysed=participants with available data for insulin dose at baseline.

Median

Full Range

international unit

Title	Denominators	Categories
	ParticipantsBG000131 ParticipantsBG001131 ParticipantsBG002

Diastolic Blood Pressure

Mean

Standard Deviation

mm Hg

Title	Denominators	Categories
	ParticipantsBG000132 ParticipantsBG001131 ParticipantsBG002

Systolic Blood Pressure

Mean

Standard Deviation

mm Hg

Title	Denominators	Categories
	ParticipantsBG000132 ParticipantsBG001131 ParticipantsBG002

Diabetes Treatment Satisfaction Questionnaire

Mean

Standard Deviation

scores on scale

Title	Denominators	Categories
	ParticipantsBG000132 ParticipantsBG001

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 in HbA1c (Glycosylated Haemoglobin)

Estimated mean change from baseline in HbA1c at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

Full analysis set included all randomised subjects who had received at least 1 dose of randomised semaglutide or placebo.

Posted

Least Squares Mean

Standard Error

percentage of glycosylated hemoglobin

Week 0, week 30

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG001	Semaglutide 1.0 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly for next 4 weeks and then semaglutide 1.0 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG002	Placebo	Subjects received placebo (matched to semaglutide) sc injection once weekly for 30 weeks. Placebo injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Units	Counts
Participants	OG000132 OG001131 OG002133

Title

Denominators

Categories

Title	Measurements
	OG000-1.45± 0.09 OG001-1.85± 0.09 OG002-0.09± 0.09

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 OG002	Hierarchical testing was performed as per sequence listed below:Change in HbA1c: semaglutide 1.0 mg vs placebo. Change in HbA1c: semaglutide 0.5 mg vs placebo. Change in body weight: semaglutide 1.0 mg vs placebo. Change in body weight: semaglutide 0.5 mg vs placebo. Analysis was performed using MMRM with treatment, country and stratification variable (HbA1c at screening [≤8.0% or >8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate	Mixed Models Analysis		< 0.0001		Treatment difference	-1.75			2-Sided	95	-2.01	-1.50			Superiority for change in HbA1c was claimed if the upper limit of the 2-sided 95% CI for the estimated difference was below 0%.

Secondary

Change in Body Weight

Estimated mean change from baseline in body weight at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

Full analysis set.

Posted

Least Squares Mean

Standard Error

Week 0, week 30

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG001	Semaglutide 1.0 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly for next 4 weeks and then semaglutide 1.0 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Secondary

Change in Fasting Plasma Glucose (FPG)

Estimated mean change from baseline in FPG at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

Full analysis set.

Posted

Least Squares Mean

Standard Error

mg/dL

week 0, week 30

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG001	Semaglutide 1.0 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly for next 4 weeks and then semaglutide 1.0 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Secondary

Change in Insulin Dose

Estimated mean change from baseline in insulin dose at week 30 was measured in terms of ratio to baseline. Responses at week 30 are analysed using an Analysis of covariance model with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using last observation carried forward.

Full analysis set

Posted

Least Squares Mean

Standard Error

ratio

week 0, week 30

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG001	Semaglutide 1.0 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly for next 4 weeks and then semaglutide 1.0 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Secondary

Change in Systolic and Diastolic Blood Pressure

Estimated mean change from baseline in systolic and diastolic blood pressure at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

Full analysis set

Posted

Least Squares Mean

Standard Error

mm Hg

week 0, week 30

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG001	Semaglutide 1.0 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly for next 4 weeks and then semaglutide 1.0 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Secondary

Patient Reported Outcomes, Diabetes Treatment Satisfaction Questionnaire (DTSQ)

The DTSQs questionnaire was used to assess subjects' treatment satisfaction and contained 8 components and evaluates the diabetes treatment (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings towards the treatment. The result presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. The post-baseline responses are analysed using an ANCOVA model with treatment, country and stratification variables (HbA1c level at screening [<= 8.0% or > 8.0%] and use of metformin [yes or no]) as fixed factors and baseline value as covariate. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using last observation carried forward.

Full analysis set

Posted

Least Squares Mean

Standard Error

scores on a scale

week 0, week 30

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG001	Semaglutide 1.0 mg

Secondary

HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association (ADA) Target

Percentage of subjects with HbA1C below 7.0% after 30 weeks treatment. Missing data imputed from a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit.

Full analysis set

Posted

Number

percentage of subjects

After 30 weeks treatment

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG001	Semaglutide 1.0 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly for next 4 weeks and then semaglutide 1.0 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG002

Secondary

HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target

Percentage of participants with HbA1c below or equal to 6.5% after 30 weeks treatment. Missing data imputed from a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit.

Full analysis set.

Posted

Number

percentage of subjects

After 30 weeks treatment

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.
OG001	Semaglutide 1.0 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly for next 4 weeks and then semaglutide 1.0 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Semaglutide 0.5 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.	8	132	52	132
EG001	Semaglutide 1.0 mg	Subjects received semaglutide 0.25 mg sc injection once weekly for 4 weeks followed by semaglutide 0.5 mg once weekly for next 4 weeks and then semaglutide 1.0 mg once weekly up to week 30. Semaglutide injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.	12	131	54	131
EG002	Placebo	Subjects received placebo (matched to semaglutide) sc injection once weekly for 30 weeks. Placebo injection was administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.	9	133	34	133

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Blood pressure increased	Investigations	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Carotid endarterectomy	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Cataract	Eye disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Coronary arterial stent insertion	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk
Coronary artery bypass	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0021 events1 affected133 at risk
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Diverticulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Drug hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Femoral artery occlusion	Vascular disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Ischaemic stroke	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Meningitis aseptic	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Peripheral artery angioplasty	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk
Peripheral artery stent insertion	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Pyelonephritis acute	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected131 at risk EG0021 events1 affected133 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Schizophrenia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk
Spondylolisthesis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected131 at risk EG0020 events0 affected133 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected131 at risk EG0020 events0 affected133 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0005 events5 affected132 at risk EG0017 events7 affected131 at risk EG0021 events1 affected133 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 events6 affected132 at risk EG0019 events9 affected131 at risk EG0022 events2 affected133 at risk
Lipase increased	Investigations	MedDRA	Systematic Assessment	EG00015 events12 affected132 at risk EG0017 events7 affected131 at risk EG0024 events4 affected133 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00014 events11 affected132 at risk EG0016 events6 affected131 at risk EG00216 events14 affected133 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00021 events15 affected132 at risk EG00123 events22 affected131 at risk EG0026 events6 affected133 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00010 events8 affected132 at risk EG0011 events1 affected131 at risk EG0024 events4 affected133 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 events2 affected132 at risk EG0015 events4 affected131 at risk EG00211 events8 affected133 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 events8 affected132 at risk EG00117 events15 affected131 at risk EG0024 events4 affected133 at risk

ID	Term
D003920	Diabetes Mellitus
D003924	Diabetes Mellitus, Type 2

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