Dose-finding of Semaglutide Administered Subcutaneously O... | NCT02461589

ID	Type	Description	Link
2014-003196-39	EudraCT Number
U1111-1159-4923	Other Identifier	WHO

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Semaglutide 0.05 mg/day	Experimental	Drug: semaglutide
Liraglutide 0.3 mg/day	Active Comparator	Drug: liraglutide
Placebo 50 µL	Placebo Comparator	Drug: placebo
Semaglutide 0.05/0.1 mg/day	Experimental	Drug: semaglutide
Liraglutide 0.3/0.6 mg/day	Active Comparator	Drug: liraglutide
Placebo 50/100 µL	Placebo Comparator	Drug: placebo
Semaglutide 0.05/0.1/0.2 mg/day	Experimental	Drug: semaglutide
Liraglutide 0.3/0.6/1.2 mg/day

Interventions

Name	Type	Description	Arm Group Labels	Other Names
semaglutide	Drug	Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in HbA1c (Glycosylated Haemoglobin)	Estimated mean change from baseline in HbA1c at week 26. The data were analysed for the "on-treatment until rescue medication" observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy.	Week 0, week 26

Secondary Outcomes

Measure	Description	Time Frame
Change in Fasting Plasma Glucose (FPG)	Estimated mean change from baseline in FPG at week 26. The data were analysed for the "on-treatment until rescue medication" observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy.	Week 0, Week 26

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, age at least 18 years at the time of signing informed consent.
Subjects should be on stable diabetes treatment consisting of diet and exercise with or without metformin (at least 1500 mg daily or maximum tolerated dose documented in the patient medical record) for at least 90 days prior to screening
HbA1c (glycosylated haemoglobin): 53-86 mmol/mol (7.0-10.0%) (both inclusive)
BMI: 25.0 - 40.0 kg/m^2 (both inclusive)

Exclusion Criteria:

Simultaneous participation in any other clinical trial of an investigational medicinal product
Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods throughout the trial including the 7 weeks follow-up period (adequate contraceptive measures as required by local regulation or practice). Germany: Only highly effective methods of birth control are accepted (i.e. 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. United Kingdom: Adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), female sterilisation, male sterilisation (where partner is sole partner of subject), or true abstinence (when in line with preferred and usual lifestyle)
Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before screening (an exception is short-term insulin treatment for acute illnesses for a total of below or equal to 14 days)
Anticipated initiation or change in concomitant medications (for more than 14 consecutive days or on an frequent basis) known to affect weight or glucose metabolism (e.g. orlistat, thyroid hormones, corticosteroids)
History of pancreatitis (acute or chronic)
Screening calcitonin above or equal to 50 ng/L
Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN2) or Medullary Thyroid Carcinoma (MTC)
Severe to moderate renal impairment defined as GFR, estimated below 60 ml/min/1.73 m^2 as per CKD-EPI (Chronic Kidney Disease Epidemiology)
Within the past 180 days before screening any of the following: Myocardial infarction, stroke or hospitalisation for unstable angina and/or transient ischemic attack
Currently planned coronary, carotid or peripheral artery revascularisation
Patients presently classified as being in New York Heart Association (NYHA) Class III or 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		Birmingham	Alabama	35209	United States
Novo Nordisk Investigational Site

PubMed Identifier	Type	Citation	Retractions
30026333	Result	Lingvay I, Desouza CV, Lalic KS, Rose L, Hansen T, Zacho J, Pieber TR. A 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin. Diabetes Care. 2018 Sep;41(9):1926-1937. doi: 10.2337/dc17-2381. Epub 2018 Jul 19.

Label	URL
Clinical Trials at Novo Nordisk	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Semaglutide 0.05 mg/Day	Participants received semaglutide 0.05 mg subcutaneous (sc) injection once daily for 26 weeks. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
FG001	Semaglutide 0.1 mg/Day

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Semaglutide 0.05 mg/Day	Participants received semaglutide 0.05 mg subcutaneous (sc) injection once daily for 26 weeks. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
BG001	Semaglutide 0.1 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
BG002	Semaglutide 0.2 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks and then semaglutide 0.2 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
BG003	Semaglutide 0.3 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks followed by 0.2 mg once daily for next 4 weeks and then semaglutide 0.3 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
BG004	Liraglutide 0.3 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 26 weeks. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
BG005	Liraglutide 0.6 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 4 weeks followed by liraglutide 0.6 mg once daily upto week 26. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
BG006	Liraglutide 1.2 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 4 weeks followed by liraglutide 0.6 mg once daily for next 4 weeks and then liraglutide 1.2 mg once daily upto week 26. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
BG007	Liraglutide 1.8 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 4 weeks followed by liraglutide 0.6 mg once daily for next 4 weeks followed by liraglutide 1.2 mg once daily for next 4 weeks and then liraglutide 1.8 mg once daily upto week 26. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
BG008	Placebo	Participants received placebo (the volume matched the volume used for the specific dose of semaglutide or liraglutide) sc injection once daily upto 26 weeks. Placebo injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
BG009	Semaglutide Flexible	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks followed by 0.2 mg once daily for next 4 weeks and then semaglutide 0.3 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals. Participants were allowed to follow a more flexible dose-escalation regimen based on gastrointestinal tolerability. Semaglutide dose levels could be reduced in participants with poor gastrointestinal tolerability depending on investigator's assessment.
BG010	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
	BG00057.53± 9.8 BG00157.51± 10.0 BG00258.37± 9.58 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00031 BG00128 BG002

HbA1c (glycosylated haemoglobin)

Mean

Standard Deviation

percentage of HbA1c

Title

Denominators

Categories

Title	Measurements
	BG0007.87± 0.71 BG0017.91± 0.83 BG002

Fasting plasma glucose

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0009.26± 2.60 BG0018.97± 2.22 BG002

Body weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00093.44± 18.27 BG00192.40± 17.20 BG002

Systolic blood pressure

Mean

Standard Deviation

mmHg

Title

Denominators

Categories

Title	Measurements
	BG000133.70± 15.14 BG001130.97± 14.92 BG002

Diastolic blood pressure

Mean

Standard Deviation

mmHg

Title

Denominators

Categories

Title	Measurements
	BG00080.06± 8.90 BG00179.71± 8.56 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)

Estimated mean change from baseline in HbA1c at week 26. The data were analysed for the "on-treatment until rescue medication" observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy.

Full analysis set

Posted

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Week 0, week 26

ID	Title	Description
OG000	Semaglutide 0.05 mg/Day	Participants received semaglutide 0.05 mg subcutaneous (sc) injection once daily for 26 weeks. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG001	Semaglutide 0.1 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG002	Semaglutide 0.2 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks and then semaglutide 0.2 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG003	Semaglutide 0.3 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks followed by 0.2 mg once daily for next 4 weeks and then semaglutide 0.3 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG004	Liraglutide 0.3 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 26 weeks. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG005	Liraglutide 0.6 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 4 weeks followed by liraglutide 0.6 mg once daily upto week 26. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG006	Liraglutide 1.2 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 4 weeks followed by liraglutide 0.6 mg once daily for next 4 weeks and then liraglutide 1.2 mg once daily upto week 26. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG007	Liraglutide 1.8 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 4 weeks followed by liraglutide 0.6 mg once daily for next 4 weeks followed by liraglutide 1.2 mg once daily for next 4 weeks and then liraglutide 1.8 mg once daily upto week 26. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG008	Placebo	Participants received placebo (the volume matched the volume used for the specific dose of semaglutide or liraglutide) sc injection once daily upto 26 weeks. Placebo injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG009	Semaglutide Flexible	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks followed by 0.2 mg once daily for next 4 weeks and then semaglutide 0.3 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals. Participants were allowed to follow a more flexible dose-escalation regimen based on gastrointestinal tolerability. Semaglutide dose levels could be reduced in participants with poor gastrointestinal tolerability depending on investigator's assessment.

Units	Counts
Participants	OG00064 OG00163 OG00265 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.97± 0.85 OG001-1.30± 1.03 OG002-1.65± 0.79 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG008		Mixed Models Analysis		<0.0001		Treatment difference	-1.04			2-Sided	95	-1.30	-0.77					Other
OG001 OG008		Mixed Models Analysis		<0.0001

Secondary

Change in Fasting Plasma Glucose (FPG)

Estimated mean change from baseline in FPG at week 26. The data were analysed for the "on-treatment until rescue medication" observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy.

Full analyses set. For "Semaglutide flexible arm", data was available only for 63 subjects.

Posted

Mean

Standard Deviation

mmol/L

Week 0, Week 26

ID	Title	Description
OG000	Semaglutide 0.05 mg/Day	Participants received semaglutide 0.05 mg subcutaneous (sc) injection once daily for 26 weeks. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG001	Semaglutide 0.1 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG002	Semaglutide 0.2 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks and then semaglutide 0.2 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.

Secondary

Body Weight Change

The data were analysed for the "on-treatment until rescue medication" observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy.

Full analysis set

Posted

Mean

Standard Deviation

Week 0, Week 26

ID	Title	Description
OG000	Semaglutide 0.05 mg/Day	Participants received semaglutide 0.05 mg subcutaneous (sc) injection once daily for 26 weeks. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG001	Semaglutide 0.1 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG002	Semaglutide 0.2 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks and then semaglutide 0.2 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.

Secondary

Change in Systolic and Diastolic Blood Pressure

Full analysis set

Posted

Mean

Standard Deviation

mmHg

Week 0, Week 26

ID	Title	Description
OG000	Semaglutide 0.05 mg/Day	Participants received semaglutide 0.05 mg subcutaneous (sc) injection once daily for 26 weeks. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG001	Semaglutide 0.1 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.
OG002	Semaglutide 0.2 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks and then semaglutide 0.2 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Semaglutide 0.05 mg/Day	Participants received semaglutide 0.05 mg subcutaneous (sc) injection once daily for 26 weeks. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.	7	64	31	64
EG001	Semaglutide 0.1 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.	3	63	34	63
EG002	Semaglutide 0.2 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks and then semaglutide 0.2 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.	2	65	39	65
EG003	Semaglutide 0.3 mg/Day	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks followed by 0.2 mg once daily for next 4 weeks and then semaglutide 0.3 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.	2	63	42	63
EG004	Liraglutide 0.3 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 26 weeks. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.	1	64	33	64
EG005	Liraglutide 0.6 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 4 weeks followed by liraglutide 0.6 mg once daily upto week 26. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.	2	64	27	64
EG006	Liraglutide 1.2 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 4 weeks followed by liraglutide 0.6 mg once daily for next 4 weeks and then liraglutide 1.2 mg once daily upto week 26. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.	2	64	35	64
EG007	Liraglutide 1.8 mg/Day	Participants received liraglutide 0.3 mg sc injection once daily for 4 weeks followed by liraglutide 0.6 mg once daily for next 4 weeks followed by liraglutide 1.2 mg once daily for next 4 weeks and then liraglutide 1.8 mg once daily upto week 26. Liraglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.	7	65	35	65
EG008	Placebo	Participants received placebo (the volume matched the volume used for the specific dose of semaglutide or liraglutide) sc injection once daily upto 26 weeks. Placebo injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals.	0	129	0	129
EG009	Semaglutide Flexible	Participants received semaglutide 0.05 mg sc injection once daily for 4 weeks followed by semaglutide 0.1 mg once daily for next 4 weeks followed by 0.2 mg once daily for next 4 weeks and then semaglutide 0.3 mg once daily upto week 26. Semaglutide injection was administered in the thigh, abdomen, or upper arm, preferably around the same time of the day irrespective of meals. Participants were allowed to follow a more flexible dose-escalation regimen based on gastrointestinal tolerability. Semaglutide dose levels could be reduced in participants with poor gastrointestinal tolerability depending on investigator's assessment.	4	64	44	64

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG0030 events0 affected63 at risk EG004
Acute myocardial infarction	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Anal fistula	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0011 events1 affected63 at risk EG0020 events0 affected65 at risk EG003
Arteriosclerosis	Vascular disorders	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Atrioventricular block complete	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Bundle branch block left	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0021 events1 affected65 at risk EG003
Carotid artery stenosis	Nervous system disorders	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Catheterisation cardiac	Investigations	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0021 events1 affected65 at risk EG003
Clear cell renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Coronary revascularisation	Surgical and medical procedures	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Cystoscopy	Investigations	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0011 events1 affected63 at risk EG0020 events0 affected65 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Dupuytren's contracture	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Endarterectomy	Surgical and medical procedures	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Endometrial hyperplasia	Reproductive system and breast disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Epiploic appendagitis	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Escherichia pyelonephritis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0011 events1 affected63 at risk EG0020 events0 affected65 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Goitre	Endocrine disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Percutaneous coronary intervention	Surgical and medical procedures	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Retinal detachment	Eye disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Seizure	Nervous system disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Sepsis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Spinal meningioma benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Stent placement	Surgical and medical procedures	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Uterine polyp	Reproductive system and breast disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Vascular graft	Surgical and medical procedures	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Ventricular fibrillation	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003
Viral infection	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0010 events0 affected63 at risk EG0020 events0 affected65 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0002 events2 affected64 at risk EG0014 events3 affected63 at risk EG0021 events1 affected65 at risk EG0033 events2 affected63 at risk EG0041 events1 affected64 at risk EG0055 events3 affected64 at risk EG0062 events2 affected64 at risk EG00713 events4 affected65 at risk EG0080 events0 affected129 at risk EG0094 events4 affected64 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0004 events2 affected64 at risk EG0014 events2 affected63 at risk EG0027 events3 affected65 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0011 events1 affected63 at risk EG0025 events4 affected65 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0003 events3 affected64 at risk EG0010 events0 affected63 at risk EG0023 events3 affected65 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0003 events3 affected64 at risk EG0014 events4 affected63 at risk EG0022 events2 affected65 at risk EG003
Bronchitis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0021 events1 affected65 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0002 events2 affected64 at risk EG0014 events4 affected63 at risk EG00211 events6 affected65 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0011 events1 affected63 at risk EG0020 events0 affected65 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19	Systematic Assessment	EG0003 events3 affected64 at risk EG0017 events7 affected63 at risk EG0026 events6 affected65 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG00010 events7 affected64 at risk EG00113 events10 affected63 at risk EG00215 events10 affected65 at risk EG003
Dizziness	Nervous system disorders	MedDRA 19	Systematic Assessment	EG0004 events2 affected64 at risk EG0016 events4 affected63 at risk EG0022 events2 affected65 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0006 events1 affected64 at risk EG0017 events5 affected63 at risk EG0028 events5 affected65 at risk EG003
Fatigue	General disorders	MedDRA 19	Systematic Assessment	EG0002 events2 affected64 at risk EG0011 events1 affected63 at risk EG0024 events4 affected65 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0002 events2 affected64 at risk EG0015 events1 affected63 at risk EG0026 events4 affected65 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0018 events4 affected63 at risk EG0023 events3 affected65 at risk EG003
Headache	Nervous system disorders	MedDRA 19	Systematic Assessment	EG00017 events7 affected64 at risk EG00130 events8 affected63 at risk EG00213 events4 affected65 at risk EG003
Hypertension	Vascular disorders	MedDRA 19	Systematic Assessment	EG0002 events2 affected64 at risk EG0014 events4 affected63 at risk EG0022 events2 affected65 at risk EG003
Lipase increased	Investigations	MedDRA 19	Systematic Assessment	EG0003 events3 affected64 at risk EG0013 events3 affected63 at risk EG0023 events3 affected65 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0001 events1 affected64 at risk EG0011 events1 affected63 at risk EG0020 events0 affected65 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 19	Systematic Assessment	EG00012 events7 affected64 at risk EG0017 events6 affected63 at risk EG0024 events4 affected65 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG00016 events11 affected64 at risk EG00120 events12 affected63 at risk EG00222 events14 affected65 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0003 events2 affected64 at risk EG0012 events2 affected63 at risk EG0020 events0 affected65 at risk EG003
Sinusitis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 events0 affected64 at risk EG0010 events0 affected63 at risk EG0021 events1 affected65 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 19	Systematic Assessment	EG0008 events7 affected64 at risk EG0012 events2 affected63 at risk EG0021 events1 affected65 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG00010 events6 affected64 at risk EG00113 events4 affected63 at risk EG0029 events6 affected65 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
D052216	Glucagon-Like Peptide 1
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists