Efficacy and Safety of Semaglutide Once-weekly Versus Sit... | NCT01930188

NCT01930188

ID	Type	Description
2012-004827-19	EudraCT Number
U1111-1135-8730	Other Identifier	WHO
132366	Other Identifier	JapicCTI
CTRI/2014/05/004626	Registry Identifier	Clinical Trial Registry India (CTRI)

Status Module

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Semaglutide 0.5 mg + sitagliptin placebo	Experimental	Drug: semaglutide Drug: placebo
Semaglutide 1.0 mg + sitagliptin placebo	Experimental	Drug: semaglutide Drug: placebo
Sitagliptin 100 mg + semaglutide placebo 1.0 mg	Active Comparator	Drug: sitagliptin Drug: placebo
Sitagliptin 100 mg + semaglutide placebo 0.5 mg	Active Comparator	Drug: sitagliptin Drug: placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
semaglutide	Drug	For subcutaneous injection (s.c., under the skin) once weekly. Will follow a fixed dose escalation regimen. The trial drug will be added on to the subject's stable pre-trial medication.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in HbA1c (Glycosylated Haemoglobin) From Baseline	Change in HbA1c from baseline until week 56.Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of randomised semaglutide or sitagliptin.	Week 0, week 56

Secondary Outcomes

Measure	Description	Time Frame
Change in Body Weight From Baseline	Change in body weight from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin.	Week 0, week 56
Change in Fasting Plasma Glucose (FPG) From Baseline

Eligibility Module

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		Buenos Aires		C1425AGC	Argentina
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30938762	Background	Fonseca VA, Capehorn MS, Garg SK, Jodar Gimeno E, Hansen OH, Holst AG, Nayak G, Seufert J. Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide. J Clin Endocrinol Metab. 2019 Sep 1;104(9):4078-4086. doi: 10.1210/jc.2018-02685.
30865526	Background

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 + Sitagliptin Placebo	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
FG001	Semaglutide 1.0 mg + Sitagliptin Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
BG001	Semaglutide 1.0 mg + Sitagliptin Placebo	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
BG002	Sitagliptin + Semaglutide Placebo	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.
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
	BG00054.8± 10.2 BG00156.0± 9.4 BG00254.6± 10.4 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000202 BG001204 BG002

HbA1c

Mean

Standard Deviation

percentage

Title

Denominators

Categories

Title	Measurements
	BG0008.01± 0.92 BG0018.04± 0.93 BG002

Body Weight

Mean

Standard Deviation

kilograms

Title

Denominators

Categories

Title	Measurements
	BG00089.93± 20.39 BG00189.21± 20.74 BG002

Fasting Plasma Glucose

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0009.33± 2.38 BG0019.29± 2.22 BG002

Diastolic and Systolic Blood Pressure

Mean

Standard Deviation

mmHg

Title

Denominators

Categories

Diastolic Blood pressure

Title	Measurements
	BG00080.63± 9.76 BG00180.87± 9.08 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 in HbA1c (Glycosylated Haemoglobin) From Baseline

Change in HbA1c from baseline until week 56.Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of randomised semaglutide or sitagliptin.

Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit.

Posted

Least Squares Mean

Standard Error

percentage of glycosylated haemoglobin

Week 0, week 56

ID	Title	Description
OG000	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG001	Semaglutide 1.0 mg + Sitagliptin Placebo	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG002	Sitagliptin + Semaglutide Placebo	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.

Units	Counts
Participants	OG000409 OG001409 OG002407

Title

Denominators

Categories

Title	Measurements
	OG000-1.32± 0.05 OG001-1.61± 0.05 OG002-0.55± 0.05

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		Mixed Models Analysis	Post-baseline responses analysed with mixed model for repeated measurements-treatment & country (fixed) & baseline (covariate) all nested within visit	<0.0001		treatment difference	-1.06			2-Sided	95	-1.21	-0.91					Non-Inferiority or Equivalence	Non-inferiority was concluded if the upper limit of the two-sided 95% confidence interval for the estimated treatment difference between semaglutide 1.0 mg and sitagliptin was below the pre-specified non-inferiority margin (0.3 %).

Secondary

Change in Body Weight From Baseline

Change in body weight from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin.

Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit.

Posted

Least Squares Mean

Standard Error

kilograms

Week 0, week 56

ID	Title	Description
OG000	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG001	Semaglutide 1.0 mg + Sitagliptin Placebo	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG002	Sitagliptin + Semaglutide Placebo	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.

Secondary

Change in Fasting Plasma Glucose (FPG) From Baseline

Change in fasting plasma glucose from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin.

Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit

Posted

Least Squares Mean

Standard Error

mg/dL

Week 0, week 56

ID	Title	Description
OG000	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG001	Semaglutide 1.0 mg + Sitagliptin Placebo	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG002	Sitagliptin + Semaglutide Placebo	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.

Secondary

Change in Systolic and Diastolic Blood Pressure From Baseline

Change in systolic and diastolic blood pressure from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin

Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit

Posted

Least Squares Mean

Standard Error

mmHg

Week 0, week 56

ID	Title	Description
OG000	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG001	Semaglutide 1.0 mg + Sitagliptin Placebo	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG002	Sitagliptin + Semaglutide Placebo	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.

Secondary

Change in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) From Baseline

Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin. The DTSQs questionnaire was used to assess subjects' treatment satisfaction. This questionnaire 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.

Out of the 1225 subjects in FAS, 76 in semaglutide 0.5 mg arm, 76 in semaglutide 1.0 mg arm, and 113 in placebo arm had missing data for the endpoint. Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit.

Posted

Least Squares Mean

Standard Error

Units on a scale

Week 0, week 56

ID	Title	Description
OG000	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG001	Semaglutide 1.0 mg + Sitagliptin Placebo

Secondary

Subjects Who Achieved HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target (Yes/no)

Subjects who achieved HbA1c ≤6.5% (48 mmol/mol) American Association of Clinical Endocrinologists (AACE) target (yes/no) after week 56 weeks of treatment.

Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin

Posted

Number

Subjects

After 56 weeks treatment

ID	Title	Description
OG000	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG001	Semaglutide 1.0 mg + Sitagliptin Placebo	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.
OG002	Sitagliptin + Semaglutide Placebo	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Semaglutide 1.0 mg + Sitagliptin Placebo	Semaglutide 1.0 mg once-weekly + Sitagliptin placebo once-daily	30	409	197	409
EG001	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 0.5 mg once-weekly + Sitagliptin placebo once-daily	30	409	208	409
EG002	Sitagliptin 100 mg + Semaglutide Placebo 1.0 mg	Sitagliptin 100 mg once-daily + Semaglutide placebo 1.0 mg once-weekly	13	204	75	204
EG003	Sitagliptin 100 mg + Semaglutide Placebo 0.5 mg	Sitagliptin 100 mg once-daily + Semaglutide placebo 0.5 mg once-weekly	16	203	85	203

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal lymphadenopathy	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG0030 events0 affected203 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Angioedema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Appendicitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0011 events1 affected409 at risk EG0021 events1 affected204 at risk EG003
Appendicitis perforated	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Atrioventricular block second degree	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Benign neoplasm of eyelid	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Calculus bladder	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Cardiovascular disorder	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Cataract	Eye disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0002 events2 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0002 events2 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Chronic gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Congestive cardiomyopathy	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Death	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Drug-induced liver injury	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Epiglottitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Gas poisoning	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Gastritis erosive	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Glycosuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Goitre	Endocrine disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Granuloma	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Haemoglobin decreased	Investigations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Haemorrhoid operation	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0012 events2 affected409 at risk EG0020 events0 affected204 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0021 events1 affected204 at risk EG003
Hypertensive emergency	Vascular disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Hypovolaemic shock	Vascular disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0022 events2 affected204 at risk EG003
Ketonuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Ligamentitis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Lymphadenitis	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Mallory-Weiss syndrome	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Meniscus operation	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Neuroendocrine carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0021 events1 affected204 at risk EG003
Osteitis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Pancreatic disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0012 events2 affected409 at risk EG0020 events0 affected204 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Pancreatitis necrotising	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Papilla of Vater stenosis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Perineal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Peripheral venous disease	Vascular disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Peritonitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Pharyngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0012 events2 affected409 at risk EG0020 events0 affected204 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Pyelonephritis chronic	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Splenic lesion	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Swollen tongue	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003
Thyroid adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Troponin I increased	Investigations	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Umbilical hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0012 events2 affected409 at risk EG0020 events0 affected204 at risk EG003
Urosepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0010 events0 affected409 at risk EG0020 events0 affected204 at risk EG003
Xanthelasma	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected409 at risk EG0011 events1 affected409 at risk EG0020 events0 affected204 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00029 events23 affected409 at risk EG00120 events18 affected409 at risk EG0025 events5 affected204 at risk EG0034 events3 affected203 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00029 events27 affected409 at risk EG00128 events26 affected409 at risk EG0026 events6 affected204 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00085 events53 affected409 at risk EG00191 events53 affected409 at risk EG00217 events13 affected204 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00027 events20 affected409 at risk EG00128 events26 affected409 at risk EG0024 events4 affected204 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00042 events29 affected409 at risk EG00181 events26 affected409 at risk EG00219 events9 affected204 at risk EG003
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG00025 events22 affected409 at risk EG00123 events18 affected409 at risk EG00214 events13 affected204 at risk EG003
Lipase increased	Investigations	MedDRA	Systematic Assessment	EG00038 events32 affected409 at risk EG00141 events33 affected409 at risk EG00216 events13 affected204 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00033 events29 affected409 at risk EG00163 events50 affected409 at risk EG00220 events19 affected204 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG000140 events72 affected409 at risk EG001110 events73 affected409 at risk EG00215 events13 affected204 at risk EG003
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00012 events10 affected409 at risk EG0017 events7 affected409 at risk EG0025 events5 affected204 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG000119 events41 affected409 at risk EG00149 events33 affected409 at risk EG0027 events6 affected204 at risk EG003

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

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines