STEP 6: Research Study Investigating How Well Semaglutide Works in People Living With Overweight or Obesity

Effect and Safety of Semaglutide Once-weekly in East Asian Subjects With Overweight or Obesity

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03811574

Acronym

STEP 6

Enrollment

401

Registered

2019-01-22

Start date

2019-01-21

Completion date

2020-11-20

Last updated

2022-03-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity, Overweight

Brief summary

This study will look at the change in participants' body weight from the start to the end of the study. This is to compare the effect on body weight in people taking semaglutide (a new medicine) and people taking dummy medicine. In addition to taking the medicine, participants will have talks with study staff about healthy food choices, how to be more physically active and what participants can do to lose weight. Participants will either get semaglutide or dummy medicine - which treatment participants get is decided by chance. Participants are three times as likely to get semaglutide as dummy medicine. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skinfold in the stomach, thigh or upper arm. The study will last for about one and a half years. Participants will have 14 clinic visits and 11 phone calls with the study doctor.

Interventions

DRUGSemaglutide

Semaglutide injections will be administered once-weekly by a pre-filled pen-injector at the same day of the week (to the extent possible). Injections may be administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals.

DRUGPlacebo (semaglutide)

Placebo (semaglutide) injections will be administered once-weekly by a pre-filled pen-injector at the same day of the week (to the extent possible). Injections may be administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Sponsor staff involved in the clinical trial is masked according to company standard procedures

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female, age more than or equal to 18 years at the time of signing informed consent * BMI more than or equal to 27.0 kg/m\^2 with more than or equal to 2 weight related comorbidities (treated or untreated) or BMI more than or equal to 35.0 kg/m\^2 with more than or equal to 1 weight related comorbidity (treated or untreated) according to the JASSO guideline. At least one comorbidity should be hypertension or dyslipidaemia (Japan only: or T2D) * History of at least one self-reported unsuccessful dietary effort to lose body weight * For subjects with T2D at screening (Japan only): a) Diagnosed with T2D more than or equal to 180 days prior to the day of screening. b) HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive)

Exclusion criteria

* A self-reported change in body weight more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records * For subjects without T2D at screening: HbA1c more than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening * For subjects with T2D at screening (Japan only): a) Renal impairment measured as estimated glomerular filtration rate (eGFR) value of less than 30 mL/min/1.73 m\^2 (less than 60 mL/min/1.73 m\^2 in subjects treated with sodium-glucose co-transporter 2 inhibitor (SGLT2i)) according to chronic kidney disease epidemiology (CKD-EPI) creatinine equation as defined by kidney disease improving global outcome (KDIGO) 2012 by the central laboratory at screening. b) Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation

Design outcomes

Primary

Measure	Time frame	Description
Change in Body Weight (%)	Baseline (week 0), week 68	Change from baseline (week 0) in body weight for 'in-trial' observation period at week 68 is presented. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%	At week 68	Number of participants who achieved greater than or equal to (≥) 5% weight loss at week 68 for in-trial observation period is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).

Secondary

Measure	Time frame	Description
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%	At week 68	Number of participants who achieved greater than or equal to (≥) 20% weight loss at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 20% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 20% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Waist Circumference Measured Midway Between the Lower Rib Margin and the Iliac Crest	Baseline (week 0) to week 68	Change in waist circumference measured midway between the lower rib margin and the iliac crest from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Waist Circumference Measured According to the JASSO (Japan Society for the Study of Obesity) Guideline	Baseline (week 0) to week 68	Change in Waist circumference measured according to the JASSO guideline from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Body Weight (Kg)	Baseline (week 0) to week 68	Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Body Mass Index (BMI)	Baseline (week 0) to week 68	Change in BMI from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Visceral Fat Area (VFA) (%)	Baseline (week 0) to week 68	Change in VFA from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Visceral Fat Area (VFA) Centimeter Square (cm^2)	Baseline (week 0) to week 68	Change in VFA from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in HbA1c (%)	Baseline (week 0) to week 68	Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in HbA1c (mmol/Mol)	Baseline (week 0) to week 68	Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Fasting Plasma Glucose	Baseline (week 0) to week 68	Change in fasting plasma glucose from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization to last trial-related subject-site contact.
Change in Fasting Serum Insulin-ratio to Baseline	Baseline (week 0) to week 68	Change in fasting serum insulin measured as milli-international units per milliliter (mIU/mL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Systolic Blood Pressure	Baseline (week 0) to week 68	Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Diastolic Blood Pressure	Baseline (week 0) to week 68	Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Total Cholesterol-ratio to Baseline	Baseline (week 0) to week 68	Change in total cholesterol measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in High-density Lipoproteins (HDL)-Ratio to Baseline	Baseline (week 0) to week 68	Change in HDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Low-density Lipoproteins (LDL)-Ratio to Baseline	Baseline (week 0) to week 68	Change in LDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization to last trial-related subject-site contact.
Change in Very Low-density Lipoproteins (VLDL)-Ratio to Baseline	Baseline (week 0) to week 68	Change in VLDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization to last trial-related subject-site contact.
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%	At week 68	Number of participants who achieved greater than or equal to (≥) 10% weight loss at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 10% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 10% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Triglycerides-ratio to Baseline	Baseline (week 0) to week 68	Change in triglycerides measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline	Baseline (week 0) to week 68	Change in hsCRP measured in milligram per ilitre (mg/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Plasminogen Activator Inhibitor-1 Activity-ratio to Baseline	Baseline (week 0) to week 68	Change in plasminogen activator inhibitor-1 (PAI-1) activity measured in arbritary units per milliliter (AU/ml) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Change in Short Form 36 v2.0 Acute (SF-36) Score	Baseline (week 0) to week 68	SF-36 is a 36-item patient-reported survey of patient health that measures participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for all the domains. The 0-100 scale scores from SF-36 were converted to norm-based scores to enable a direct interpretation in relation to distribution of scores in the 2009 U.S. general population. In metric of norm-based scores, 50 and 10 corresponds to mean and standard deviation respectively. Change from week 0 in domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on data from in-trial observation period which is uninterrupted time interval from randomisation to last contact with trial site.
Change in Impact of Weight on Quality of Life-lite for Clinical Trials (IWQOL-Lite for CT) Score	Baseline (week 0) to week 68	The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical function score' physical and psychosocial domains, and for total'. The endpoint was evaluated based on the data from in-trial observation period which is the uninterrupted time interval from randomisation to last contact with trial site.
Number of Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score	At week 68	The number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on 3.7 threshold. The threshold of 3.7 is specific for overweight or obese population included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, Yes infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and No infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomisation to last contact with trial site.
Number of Participants Who Achieve (Yes/no): Responder Definition Value for IWQoL-Lite for CT Physical Function (5-items) Score	At week 68	The number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on thresholds of 14.6. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, Yes infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and No infers the number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomisation to last contact with trial site.
Number of Participants Who Achieved (Yes/no): HbA1c <7.0% (53 mmol/Mol)	At week 68	Number of participants who achieved HbA1c \<7% (53 mmol/mol) at week 68 is presented. In the reported data, Yes infers the number of participants who have achieved HbA1c values less than the 7% and No infers the number of participants who have not achieved HbA1c values less than the 7%. The endpoint was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Number of Participants Who Achieved (Yes/no): HbA1c ≤6.5% (48 mmol/Mol)	At week 68	Number of participants who achieved HbA1c ≤6.5% (48 mmol/mol) at week 68 is presented. In the reported data, Yes infers the number of participants who have achieved HbA1c values less than or equal to 6.5% and No infers the number of participants who have not achieved HbA1c values less than or equal to 6.5%. The endpoint was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Number of Treatment-emergent AEs	Week 0 to week 75	An adverse event (AE) 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 with onset during the on-treatment observation period. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Number of Serious Adverse Events	Week 0 to week 75	A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. SAE results occurred from week 0 to week 75 is presented based on the on-treatment observation, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemia Episodes	Week 0 to week 75	Hypoglycaemic episodes with onset during on-treatment observation period were considered treatment-emergent. Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemia episodes with onset during on-treatment observation period were presented. Severe hypoglycaemia: episode requiring assistance of another person to administer carbohydrate, glucagon or take other corrective actions. plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by low PG concentration. BG confirmed symptomatic hypoglycaemia: episode that is BG confirmed by PG value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. On-treatment observation period is interval from date of first trial product administration (week 0) to date of last trial product administration (week 68) plus 7-week follow-up period and excluding any off-treatment time intervals.
Change in Pulse	Baseline (week 0) to week 68	Change in pulse from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.
Change in Amylase: Ratio to Baseline	Baseline (week 0) to week 68	Change in amylase measured in units/liter (U/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.
Change in Lipase: Ratio to Baseline	Baseline (week 0) to week 68	Change in lipase measured in units/litre (U/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.
Change in Calcitonin: Ratio to Baseline	Baseline (week 0) to week 68	Change in calcitonin measured in nanogram/litre (ng/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.
Change in QTCF Interval	Baseline (week 0) to week 68	Change in QTCF Interval from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.
Change in Free Fatty Acids-ratio to Baseline	Baseline (week 0) to week 68	Change in free fatty acids measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%	At week 68	Number of participants who achieved greater than or equal to (≥) 15% weight loss at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 15% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 15% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization to last trial-related subject-site contact.

Countries

Japan, South Korea

Participant flow

Recruitment details

The trial was conducted at 28 sites in 2 countries as follows (all sites screened and randomized):Japan (22 sites) and South korea (6 sites).

Pre-assignment details

The trial has a 68-week treatment period (12 weeks of dose escalation and 56 weeks of maintenance dose for 1.7 milligram (mg) once weekly arm and 16 weeks of dose escalation and 52 weeks of maintenance dose for 2.4 mg once weekly arm). Participants were randomised in 4:1:2:1 ratio to receive either semaglutide subcutaneously (s.c.) 2.4 mg once-weekly, semaglutide placebo once-weekly, semaglutide s.c. 1.7 mg once-weekly or semaglutide placebo once-weekly.

Participants by arm

Arm	Count
Semaglutide 1.7 mg Participants were to receive once-weekly s.c. injection of 0.25 mg semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.	101
Semaglutide 2.4 mg Participants were to receive once-weekly s.c. injection of 0.25 mg semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg once-weekly after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.	199
Placebo Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	101
Total	401

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Withdrawal by Subject	2	4	0

Baseline characteristics

Characteristic	Semaglutide 1.7 mg	Semaglutide 2.4 mg	Placebo	Total
Age, Continuous	51 Years STANDARD_DEVIATION 10	52 Years STANDARD_DEVIATION 12	50 Years STANDARD_DEVIATION 9	51 Years STANDARD_DEVIATION 11
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	101 Participants	199 Participants	101 Participants	401 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	101 Participants	199 Participants	101 Participants	401 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Female	37 Participants	85 Participants	26 Participants	148 Participants
Sex: Female, Male Male	64 Participants	114 Participants	75 Participants	253 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 100	0 / 199	0 / 101
other Total, other adverse events	73 / 100	142 / 199	49 / 101
serious Total, serious adverse events	7 / 100	10 / 199	7 / 101

Outcome results

Primary

Change in Body Weight (%)

Change from baseline (week 0) in body weight for 'in-trial' observation period at week 68 is presented. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).

Time frame: Baseline (week 0), week 68

Population: FAS which comprised all randomised participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Semaglutide 1.7 mg	Change in Body Weight (%)	-9.9 Percentage change	Standard Deviation 7.8
Semaglutide 2.4 mg	Change in Body Weight (%)	-13.4 Percentage change	Standard Deviation 8.6
Placebo	Change in Body Weight (%)	-1.9 Percentage change	Standard Deviation 5.9

Comparison: Treatment policy estimandp-value: <0.000195% CI: [-9.62, -5.43]ANCOVA

Comparison: Treatment policy estimandp-value: <0.000195% CI: [-12.88, -9.24]ANCOVA

Primary

Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%

Number of participants who achieved greater than or equal to (≥) 5% weight loss at week 68 for in-trial observation period is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).

Time frame: At week 68

Population: FAS which comprised all randomised participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Semaglutide 1.7 mg	Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%	Yes	71 Participants
Semaglutide 1.7 mg	Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%	No	27 Participants
Semaglutide 2.4 mg	Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%	Yes	160 Participants
Semaglutide 2.4 mg	Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%	No	33 Participants
Placebo	Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%	Yes	21 Participants
Placebo	Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%	No	79 Participants

Comparison: Treatment policy estimandp-value: <0.000195% CI: [5.53, 22.22]Regression, Logistic

Comparison: Treatment policy estimandp-value: <0.000195% CI: [11.27, 41.86]Regression, Logistic

Secondary

Change in Amylase: Ratio to Baseline

Change in amylase measured in units/liter (U/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.