Trial Outcomes & Findings for A Trial Comparing the Safety and Efficacy of Semaglutide Once Weekly Versus Sitagliptin Once Daily in Japanese Subjects With Type 2 Diabetes (NCT NCT02254291)

Last Updated: 2018-09-13

Results Overview

An adverse events (AEs) was defined as any unfavourable 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 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

308 participants

Primary outcome timeframe

Weeks 0-30

Results posted on

2018-09-13

Participant Flow

The trial was conducted at 25 sites in Japan. These sites randomised/assigned subjects to treatment.

Subjects were either on stable diet and exercise therapy only or on stable oral anti-diabetic drug (OAD) monotherapy (a maximum dose of 750 mg metformin or 2250 mg METGLUCO according to approved Japanese labelling) in addition to stable diet and exercise therapy for at least 30 days prior to screening (week -8 or week -2).

Participant milestones

Participant milestones
Measure	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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Sitagliptin The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
Overall Study STARTED	103	102	103
Overall Study Exposed	103	102	103
Overall Study COMPLETED	103	99	101
Overall Study NOT COMPLETED	0	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Sitagliptin The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
Overall Study Withdrawal by Subject	0	3	1
Overall Study Missing follow-up information	0	0	1

Baseline Characteristics

A Trial Comparing the Safety and Efficacy of Semaglutide Once Weekly Versus Sitagliptin Once Daily in Japanese Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Semaglutide 0.5 mg n=103 Participants 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Semaglutide 1.0 mg n=102 Participants 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Sitagliptin n=103 Participants The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Total n=308 Participants Total of all reporting groups
Age, Continuous	58.8 years STANDARD_DEVIATION 10.4 • n=5 Participants	58.1 years STANDARD_DEVIATION 11.6 • n=7 Participants	57.9 years STANDARD_DEVIATION 10.1 • n=5 Participants	58.3 years STANDARD_DEVIATION 10.7 • n=4 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	27 Participants n=7 Participants	22 Participants n=5 Participants	73 Participants n=4 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	75 Participants n=7 Participants	81 Participants n=5 Participants	235 Participants n=4 Participants
Glycosylated haemoglobin (HbA1c)	8.23 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.02 • n=5 Participants	8.01 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.85 • n=7 Participants	8.20 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.89 • n=5 Participants	8.15 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.93 • n=4 Participants

PRIMARY outcome

Timeframe: Weeks 0-30

Population: The safety analysis set (SAS) included all subjects receiving at least one dose of trial product and subjects contributed to the evaluation "as treated".

Outcome measures

Outcome measures
Measure	Semaglutide 0.5 mg n=103 Participants 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Semaglutide 1.0 mg n=102 Participants 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Sitagliptin n=103 Participants The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
Number of Treatment Emergent Adverse Events (TEAEs)	228 Number of events	197 Number of events	186 Number of events

SECONDARY outcome

Timeframe: Weeks 0-30

Population: The safety analysis set (SAS) included all subjects receiving at least one dose of trial product and subjects contributed to the evaluation "as treated".

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 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

Outcome measures

Outcome measures
Measure	Semaglutide 0.5 mg n=103 Participants 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Semaglutide 1.0 mg n=102 Participants 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Sitagliptin n=103 Participants The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes	0 Number of episodes	1 Number of episodes	0 Number of episodes

SECONDARY outcome

Timeframe: Week 0 and week 30

Population: 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 30.

Mean changes in HbA1c values from baseline after 30 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.

Outcome measures

Outcome measures
Measure	Semaglutide 0.5 mg n=103 Participants 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Semaglutide 1.0 mg n=102 Participants 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Sitagliptin n=103 Participants The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
Change in Glycosylated Haemoglobin A1c (HbA1c)	-1.87 Percentage of glycosylated haemoglobin Standard Error 0.07	-2.18 Percentage of glycosylated haemoglobin Standard Error 0.07	-0.74 Percentage of glycosylated haemoglobin Standard Error 0.07

Adverse Events

Semaglutide 0.5 mg

Serious events: 6 serious events

Other events: 53 other events

Deaths: 0 deaths

Semaglutide 1.0 mg

Serious events: 2 serious events

Other events: 46 other events

Deaths: 0 deaths

Sitagliptin

Serious events: 2 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Semaglutide 0.5 mg n=103 participants at risk 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Semaglutide 1.0 mg n=102 participants at risk 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Sitagliptin n=103 participants at risk The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
Cardiac disorders Angina pectoris	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Psychiatric disorders Bipolar disorder	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.98% 1/102 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Hepatobiliary disorders Cholecystitis	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.98% 1/102 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Surgical and medical procedures Coronary arterial stent insertion	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Infections and infestations Herpes zoster	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Nervous system disorders Loss of consciousness	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma stage IV	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Infections and infestations Pneumonia	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Renal and urinary disorders Postrenal failure	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Reproductive system and breast disorders Prostatitis	0.97% 1/103 • Number of events 1 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/102 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".

Other adverse events

Other adverse events
Measure	Semaglutide 0.5 mg n=103 participants at risk 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Semaglutide 1.0 mg n=102 participants at risk 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 duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 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. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	Sitagliptin n=103 participants at risk The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
Gastrointestinal disorders Abdominal discomfort	3.9% 4/103 • Number of events 4 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	6.9% 7/102 • Number of events 8 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Investigations Amylase increased	5.8% 6/103 • Number of events 7 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	2.0% 2/102 • Number of events 2 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	1.9% 2/103 • Number of events 2 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Gastrointestinal disorders Constipation	14.6% 15/103 • Number of events 16 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	11.8% 12/102 • Number of events 12 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	3.9% 4/103 • Number of events 4 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Metabolism and nutrition disorders Decreased appetite	8.7% 9/103 • Number of events 10 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	7.8% 8/102 • Number of events 8 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Gastrointestinal disorders Diarrhoea	6.8% 7/103 • Number of events 9 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	8.8% 9/102 • Number of events 14 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	1.9% 2/103 • Number of events 3 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Investigations Lipase increased	9.7% 10/103 • Number of events 12 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	6.9% 7/102 • Number of events 8 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	3.9% 4/103 • Number of events 5 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Infections and infestations Nasopharyngitis	16.5% 17/103 • Number of events 21 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	17.6% 18/102 • Number of events 22 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	29.1% 30/103 • Number of events 42 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".
Gastrointestinal disorders Nausea	10.7% 11/103 • Number of events 12 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	12.7% 13/102 • Number of events 22 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".	0.00% 0/103 • All AEs presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 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 subjects receiving at least one dose of the trial product and subjects contributed to the evaluation "as treated".

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee "At the end of the trial, one or more scientific publications may be prepared collaboratively by the Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property".
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