A Trial Comparing the Safety and Efficacy of Semaglutide... | NCT02207374

ID	Type	Description	Link
U1111-1140-3081	Other Identifier	WHO
JapicCTI-142640	Registry Identifier	JAPIC

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Semaglutide 0.5 mg	Experimental		Drug: semaglutide
Semaglutide 1.0 mg	Experimental		Drug: semaglutide
One additional OAD + pre-trial treatment	Active Comparator	The type and dosage of the additional OAD will be selected by the investigators according to the approved Japanese labelling including drug combinations and contraindications. One of DPP-4 inhibitor (dipeptidyl peptidase-4), SU (sulfonylurea), glinide, biguanide, α-GI (α-glucosidase inhibitor)or TZD (thiazolidinediones) will be selected as the additional OAD. For the subjects treated with OAD monotherapy as pre-trial treatment, the type and dosage of the additional OAD with a different mechanism of action from the pre-trial OAD should be chosen.	Drug: DPP-4 inhibitor

Interventions

Name	Type	Description	Arm Group Labels	Other Names
semaglutide	Drug	Subject will receive either a dose of 0.5 or 1.0 mg of semaglutide once weekly (subcutaneous (s.c.) injection).Treatment duration 56 weeks.	Semaglutide 0.5 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Treatment Emergent Adverse Events (TEAEs)	An adverse event (AEs) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).	Weeks 0-56

Secondary Outcomes

Measure	Description	Time Frame
Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes	Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <56 mg/dL (3.1 mmol/L), with symptoms consistent with hypoglycaemia. Severe hypoglycaemia: was an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The episodes mentioned here are treatment emergent hypoglycaemic episodes and defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, age at least 20 years at the time of signing informed consent
HbA1c (glycosylated haemoglobin A1c) between 7.0% and 10.5% (53-91 mmol/mol) (both inclusive)
Japanese subjects with type 2 diabetes mellitus (diagnosed clinically) and on stable treatment (defined as unchanged medication and unchanged dose) who are: a) on diet and exercise therapy for at least 30 days before Visit 1 (week -2). or b) on OAD monotherapy (either of SU (sulfonylurea), glinide, a-GI (a-glucosidase inhibitor) or TZD (thiazolidinediones)) within approved Japanese labelling in addition to diet and exercise therapy for at least 60 days before Visit 1 (week -2)

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 (e.g., abstinence [not having sex], diaphragm, condom [by the partner], intrauterine device, sponge, spermicide or oral contraceptives) throughout the trial including the 5 week follow-up period
Treatment with glucose lowering agent(s) other than stated in the inclusion criteria within 60 days before Visit 1 (week -2) and treatment with once weekly glucagon-like peptide-1 (GLP-1) receptor agonists within 90 days before Visit 1 (week -2). An exception is short-term treatment (below or equal to 7 days in total) with insulin in connection with inter-current illness
Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol
History of chronic or idiopathic acute pancreatitis
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 type 2 (MEN2)
Impaired renal function defined as estimated glomerular filtration rate (eGFR) 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 (Visit 2 [week 0])
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		Akita-shi, Akita		010 8543	Japan
Novo Nordisk Investigational Site

PubMed Identifier	Type	Citation	Retractions
29322610	Result	Kaku K, Yamada Y, Watada H, Abiko A, Nishida T, Zacho J, Kiyosue A. Safety and efficacy of once-weekly semaglutide vs additional oral antidiabetic drugs in Japanese people with inadequately controlled type 2 diabetes: A randomized trial. Diabetes Obes Metab. 2018 May;20(5):1202-1212. doi: 10.1111/dom.13218. Epub 2018 Feb 21.
29748996

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 were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly 0.5 mg maintenance dose for 52 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout 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 were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly 0.5 mg maintenance dose for 52 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout the trial.
BG001	Semaglutide 1.0 mg	Subjects were randomized to receive semaglutide 1.0 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly doses of 0.5 mg for 4 weeks, and finally escalated to once weekly 1.0 mg maintenance dose for 48 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout the trial.
BG002	Additional OAD	Subjects were randomised to receive one additional OAD in addition to the pre-trial treatment for a duration of 56 weeks. The type and dosage of the additional OAD was selected by the investigator according to the approved Japanese labelling based on drug combinations and contraindications. One of the following OADs was to be selected as the additional OAD therapy: dipeptidyl peptidase-4 (DPP-4) inhibitor, SU, glinide, biguanide, α-GI and TZD. For subjects treated with OAD as pre-trial treatment, the type and dosage of the additional OAD with a different mechanism of action from the pre-trial OAD was to be chosen. The dose of the additional OAD was optimized within approved Japanese labelling until week 8 (dose adjustment period) and the dose remained unchanged until week 56 (maintenance dose) unless rescue medication was needed. The type of the additional OAD remained unchanged 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

Title	Measurements
	BG00058.0± 10.6 BG00158.7± 10.2 BG00259.2± 10.1 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00073 BG00167 BG002

Glycosylated haemoglobin (HbA1c)

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.04± 0.89 BG0018.14± 0.96 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

Number of Treatment Emergent Adverse Events (TEAEs)

An adverse event (AEs) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

The safety analysis set (SAS) included all randomised subjects who had received at least one dose of semaglutide 0.5 mg (s.c.), semaglutide 1.0 mg (s.c.) or one additional OAD. Subjects in the SAS contributed to the evaluation "as treated".

Posted

Number

Number of events

Weeks 0-56

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly 0.5 mg maintenance dose for 52 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout the trial.
OG001	Semaglutide 1.0 mg	Subjects were randomized to receive semaglutide 1.0 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly doses of 0.5 mg for 4 weeks, and finally escalated to once weekly 1.0 mg maintenance dose for 48 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout the trial.
OG002	Additional OAD	Subjects were randomised to receive one additional OAD in addition to the pre-trial treatment for a duration of 56 weeks. The type and dosage of the additional OAD was selected by the investigator according to the approved Japanese labelling based on drug combinations and contraindications. One of the following OADs was to be selected as the additional OAD therapy: dipeptidyl peptidase-4 (DPP-4) inhibitor, SU, glinide, biguanide, α-GI and TZD. For subjects treated with OAD as pre-trial treatment, the type and dosage of the additional OAD with a different mechanism of action from the pre-trial OAD was to be chosen. The dose of the additional OAD was optimized within approved Japanese labelling until week 8 (dose adjustment period) and the dose remained unchanged until week 56 (maintenance dose) unless rescue medication was needed. The type of the additional OAD remained unchanged during the trial.

Units	Counts
Participants	OG000239 OG001241 OG002120

Title

Denominators

Categories

Title	Measurements
	OG000909 OG001954 OG002269

Secondary

Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes

Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <56 mg/dL (3.1 mmol/L), with symptoms consistent with hypoglycaemia. Severe hypoglycaemia: was an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The episodes mentioned here are treatment emergent hypoglycaemic episodes and defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

Posted

Number

Number of episodes

Weeks 0-56

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly 0.5 mg maintenance dose for 52 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout the trial.

Secondary

Change in Glycosylated Haemoglobin A1c (HbA1c)

The observed mean change in HbA1c values from baseline after 56 weeks of treatment. Changes in HbA1c were analysed using a mixed model for repeated measurements (MMRM) with treatment and pre-trial treatment at screening as fixed factors and baseline value as covariate. The data were analysed for the "on-treatment without rescue medication" observation period which includes observations noted at or after the date of first dose of randomised treatment and not after the last dose of the trial product (+ a 7-day visit window) or initiation of rescue medication.

The full analysis set (FAS) included all randomised subjects who have received at least one dose of trial product. All subjects contributed to the statistical model of the data analysis, but not all subjects had a value at week 56.

Posted

Least Squares Mean

Standard Error

Percentage (%) of HbA1c

Week 0, week 56

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly 0.5 mg maintenance dose for 52 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout 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 were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly 0.5 mg maintenance dose for 52 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout the trial.	19	239	160	239
EG001	Semaglutide 1.0 mg	Subjects were randomized to receive semaglutide 1.0 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly doses of 0.5 mg for 4 weeks, and finally escalated to once weekly 1.0 mg maintenance dose for 48 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout the trial.	12	241	169	241
EG002	Additional OAD	Subjects were randomised to receive one additional OAD in addition to the pre-trial treatment for a duration of 56 weeks. The type and dosage of the additional OAD was selected by the investigator according to the approved Japanese labelling based on drug combinations and contraindications. One of the following OADs was to be selected as the additional OAD therapy: dipeptidyl peptidase-4 (DPP-4) inhibitor, SU, glinide, biguanide, α-GI and TZD. For subjects treated with OAD as pre-trial treatment, the type and dosage of the additional OAD with a different mechanism of action from the pre-trial OAD was to be chosen. The dose of the additional OAD was optimized within approved Japanese labelling until week 8 (dose adjustment period) and the dose remained unchanged until week 56 (maintenance dose) unless rescue medication was needed. The type of the additional OAD remained unchanged during the trial.	8	120	61	120

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0010 events0 affected241 at risk EG0021 events1 affected120 at risk
Anal fistula	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0010 events0 affected241 at risk EG0021 events1 affected120 at risk
Benign neoplasm of prostate	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Beta haemolytic streptococcal infection	Infections and infestations	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Cardiac failure	Cardiac disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0021 events1 affected120 at risk
Cellulitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0010 events0 affected241 at risk EG0021 events1 affected120 at risk
Colon adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Constipation	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Diffuse large B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0010 events0 affected241 at risk EG0021 events1 affected120 at risk
Drowning	General disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0010 events0 affected241 at risk EG0021 events1 affected120 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Haemorrhoid operation	Surgical and medical procedures	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0010 events0 affected241 at risk EG0021 events1 affected120 at risk
Herpes zoster	Infections and infestations	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Joint arthroplasty	Surgical and medical procedures	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0012 events2 affected241 at risk EG0020 events0 affected120 at risk
Limb traumatic amputation	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Pancreatic carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0021 events1 affected120 at risk
Percutaneous coronary intervention	Surgical and medical procedures	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Peripheral artery angioplasty	Surgical and medical procedures	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Peripheral revascularisation	Surgical and medical procedures	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Peritonsillar abscess	Infections and infestations	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0010 events0 affected241 at risk EG0022 events1 affected120 at risk
Pneumonia	Infections and infestations	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Pyelonephritis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk
Varicose vein operation	Surgical and medical procedures	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected241 at risk EG0020 events0 affected120 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected241 at risk EG0020 events0 affected120 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG00015 events15 affected239 at risk EG00116 events15 affected241 at risk EG0020 events0 affected120 at risk
Amylase increased	Investigations	MedDRA 18	Systematic Assessment	EG0008 events7 affected239 at risk EG00115 events13 affected241 at risk EG0021 events1 affected120 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18	Systematic Assessment	EG00010 events9 affected239 at risk EG00113 events13 affected241 at risk EG00210 events10 affected120 at risk
Constipation	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG00049 events44 affected239 at risk EG00140 events36 affected241 at risk EG0025 events5 affected120 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18	Systematic Assessment	EG00022 events18 affected239 at risk EG00136 events32 affected241 at risk EG0020 events0 affected120 at risk
Diabetic retinopathy	Eye disorders	MedDRA 18	Systematic Assessment	EG00011 events11 affected239 at risk EG00116 events16 affected241 at risk EG0026 events6 affected120 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG00033 events24 affected239 at risk EG00149 events38 affected241 at risk EG0029 events8 affected120 at risk
Gastroenteritis	Infections and infestations	MedDRA 18	Systematic Assessment	EG00016 events15 affected239 at risk EG0016 events5 affected241 at risk EG0022 events2 affected120 at risk
Lipase increased	Investigations	MedDRA 18	Systematic Assessment	EG00025 events21 affected239 at risk EG00136 events33 affected241 at risk EG0022 events2 affected120 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG000132 events81 affected239 at risk EG001105 events75 affected241 at risk EG00260 events41 affected120 at risk
Nausea	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG00038 events29 affected239 at risk EG00170 events46 affected241 at risk EG0021 events1 affected120 at risk
Pharyngitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG00015 events12 affected239 at risk EG0019 events9 affected241 at risk EG0023 events2 affected120 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG00017 events13 affected239 at risk EG00121 events14 affected241 at risk EG0022 events2 affected120 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

ID	Term
D011480	Protease Inhibitors
D004791	Enzyme Inhibitors
D045504	Molecular Mechanisms of Pharmacological Action
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D007004	Hypoglycemic Agents
D045505	Physiological Effects of Drugs

ID	Term
C000591245	semaglutide
D054873	Dipeptidyl-Peptidase IV Inhibitors