Research Study Investigating How Well Semaglutide Works in People With Type 2 Diabetes Suffering From Overweight or Obesity

Obesity Clinical Trial

— STEP 2  

Official title:

Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity and Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03552757
• Other study ID #: NN9536-4374
• Secondary ID: U1111-1200-81482
• Status: Completed
• Phase: Phase 3
• Start date: June 4, 2018
• Est. completion date: May 1, 2020

Study information

• Verified date: November 2021
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will look at the change in the participant's 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 study medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what else the participant can do to lose weight. Overweight and obesity is associated with an increased risk of type 2 diabetes. Therefore, weight loss has shown to have a beneficial impact on the blood sugar levels. The participant will either get semaglutide or "dummy" medicine - which treatment the participant get is decided by chance. The participant will need to take 2 injections at the same time once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The study will last for about 1.5 years

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1210
• Est. completion date: May 1, 2020
• Est. primary completion date: March 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent

• Body Mass Index (BMI) greater than or equal to 27 kg/m^2 '

• History of at least one self-reported unsuccessful dietary effort to lose body weight

• Diagnosed with type 2 diabetes (haemoglobin A1c 7-10% (53-86 mmol/mol) (both inclusive)) 180 days or longer prior to the day of screening

Exclusion Criteria:

• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

• 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 Cotransporter 2 Inhibitors) according to chronic kidney disease (CKD)-Epidemiology Collaboration (EPI) creatinine equation as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 by the central laboratory at screening

• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (e.g. optometrist) within the past 90 days prior to screening or in the period between screening and randomisation

Related Conditions & MeSH terms

• Obesity
• Overweight

Intervention

Drug:
• Semaglutide 1.0 mg
Subcutaneous (s.c.) injections of semaglutide once weekly at an escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week). The dose will be escalated to next level every 4 weeks.
• Semaglutide 2.4 mg
Subcutaneous injections of semaglutide once weekly at an escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week, 1.7 mg/week and 2.4 mg/week). The dose will be escalated to next level every 4 weeks.
• Placebo I (Semaglutide)
S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide 2.4 mg (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week, 1.7 mg/week and 2.4 mg/week). The dose will be escalated to next level every 4 weeks.
• Placebo II (Semaglutide)
S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide 1.0 mg (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week). The dose will be escalated to next level every 4 weeks.

Locations

Country	Name	City	State
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Chacabuco
Argentina	Novo Nordisk Investigational Site	Córdoba
Argentina	Novo Nordisk Investigational Site	Mendoza
Argentina	Novo Nordisk Investigational Site	Santiago del Estero
Canada	Novo Nordisk Investigational Site	Calgary	Alberta
Canada	Novo Nordisk Investigational Site	Concord	Ontario
Canada	Novo Nordisk Investigational Site	London	Ontario
Canada	Novo Nordisk Investigational Site	Montreal	Quebec
Canada	Novo Nordisk Investigational Site	Montreal	Quebec
Canada	Novo Nordisk Investigational Site	Mount Pearl	Newfoundland and Labrador
Canada	Novo Nordisk Investigational Site	St-Marc-des-Carrières	Quebec
Canada	Novo Nordisk Investigational Site	Stoney Creek	Ontario
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Germany	Novo Nordisk Investigational Site	Essen
Germany	Novo Nordisk Investigational Site	Falkensee
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Lingen
Germany	Novo Nordisk Investigational Site	Münster
Germany	Novo Nordisk Investigational Site	Rehlingen-Siersburg
Germany	Novo Nordisk Investigational Site	Schweinfurt
Germany	Novo Nordisk Investigational Site	Stuttgart
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Haidari-Athens
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
India	Novo Nordisk Investigational Site	Ahmedabad	Gujarat
India	Novo Nordisk Investigational Site	Ahmedabad	Gujarat
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Coimbatore	Tamil Nadu
India	Novo Nordisk Investigational Site	Jaipur	Rajasthan
India	Novo Nordisk Investigational Site	Kochi	Kerala
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	New Dehli	New Delhi
India	Novo Nordisk Investigational Site	New Delhi
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Secunderabad
Japan	Novo Nordisk Investigational Site	Chiba-shi, Chiba
Japan	Novo Nordisk Investigational Site	Chuo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Fukuoka-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Hokkaido
Japan	Novo Nordisk Investigational Site	Hokkaido
Japan	Novo Nordisk Investigational Site	Ibaraki
Japan	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka
Japan	Novo Nordisk Investigational Site	Mitaka-shi, Tokyo
Japan	Novo Nordisk Investigational Site	Osaka
Japan	Novo Nordisk Investigational Site	Osaka
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Tochigi
Puerto Rico	Novo Nordisk Investigational Site	San Juan
Russian Federation	Novo Nordisk Investigational Site	Barnaul
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Saint Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Tomsk
South Africa	Novo Nordisk Investigational Site	Brits	North West
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
Spain	Novo Nordisk Investigational Site	Almeria
Spain	Novo Nordisk Investigational Site	Córdoba
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Málaga
Spain	Novo Nordisk Investigational Site	San Cristóbal de La Laguna
Spain	Novo Nordisk Investigational Site	Sevilla
Spain	Novo Nordisk Investigational Site	Sevilla
Spain	Novo Nordisk Investigational Site	Valladolid
United Arab Emirates	Novo Nordisk Investigational Site	Dubai
United Arab Emirates	Novo Nordisk Investigational Site	Dubai
United Arab Emirates	Novo Nordisk Investigational Site	Dubai
United Arab Emirates	Novo Nordisk Investigational Site	Hatta
United Arab Emirates	Novo Nordisk Investigational Site	Umm Al Quwain
United Kingdom	Novo Nordisk Investigational Site	Chester
United Kingdom	Novo Nordisk Investigational Site	Crewe
United Kingdom	Novo Nordisk Investigational Site	Glasgow
United Kingdom	Novo Nordisk Investigational Site	Harrogate, North Yorkshire
United Kingdom	Novo Nordisk Investigational Site	Leicester
United Kingdom	Novo Nordisk Investigational Site	Middlesbrough
United Kingdom	Novo Nordisk Investigational Site	Soham
United Kingdom	Novo Nordisk Investigational Site	Stevenage
United Kingdom	Novo Nordisk Investigational Site	Watford
United Kingdom	Novo Nordisk Investigational Site	Wellingborough
United States	Novo Nordisk Investigational Site	Alpharetta	Georgia
United States	Novo Nordisk Investigational Site	Anderson	South Carolina
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Bristol	Tennessee
United States	Novo Nordisk Investigational Site	Buena Park	California
United States	Novo Nordisk Investigational Site	Butte	Montana
United States	Novo Nordisk Investigational Site	Chapel Hill	North Carolina
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Clearwater	Florida
United States	Novo Nordisk Investigational Site	Concord	California
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Golden	Colorado
United States	Novo Nordisk Investigational Site	Greensboro	North Carolina
United States	Novo Nordisk Investigational Site	Greenville	North Carolina
United States	Novo Nordisk Investigational Site	Hickory	North Carolina
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Kissimmee	Florida
United States	Novo Nordisk Investigational Site	Lawrenceville	New Jersey
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Lomita	California
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Louisville	Kentucky
United States	Novo Nordisk Investigational Site	Minneapolis	Minnesota
United States	Novo Nordisk Investigational Site	Mission Hills	California
United States	Novo Nordisk Investigational Site	Mount Pleasant	South Carolina
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	Olive Branch	Mississippi
United States	Novo Nordisk Investigational Site	Olympia	Washington
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	Saint George	Utah
United States	Novo Nordisk Investigational Site	Saint Petersburg	Florida
United States	Novo Nordisk Investigational Site	Salisbury	North Carolina
United States	Novo Nordisk Investigational Site	Shavano Park	Texas
United States	Novo Nordisk Investigational Site	Spring Valley	California
United States	Novo Nordisk Investigational Site	Springfield	Illinois
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Tarzana	California
United States	Novo Nordisk Investigational Site	Topeka	Kansas
United States	Novo Nordisk Investigational Site	Wadsworth	Ohio
United States	Novo Nordisk Investigational Site	West Des Moines	Iowa
United States	Novo Nordisk Investigational Site	Wilmington	North Carolina
United States	Novo Nordisk Investigational Site	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Germany,  Greece,  India,  Japan,  Puerto Rico,  Russian Federation,  South Africa,  Spain,  United Arab Emirates,  United Kingdom, 

References & Publications (2)

Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I; STEP 2 Study Group. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a ra — View Citation

Kushner RF, Calanna S, Davies M, Dicker D, Garvey WT, Goldman B, Lingvay I, Thomsen M, Wadden TA, Wharton S, Wilding JPH, Rubino D. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring). 2020 Jun;28(6):1050-1061. doi: 10.1002/oby.22794. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo	Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75). 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 2-week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.	Baseline (week 0) to week 68
Primary	Participants Who Achieve (Yes/no): Body Weight Reduction =5% - Semaglutide 2.4 mg Versus Placebo	Number of participants who achieved weight reduction =5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. 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 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.	At week 68
Secondary	Change in Body Weight (%) - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg	Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Participants Who Achieve (Yes/no): Body Weight Reduction =5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg	Number of participants who achieved weight reduction =5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	At week 68
Secondary	Change in Waist Circumference	Change in waist circumference from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Body Weight (Kg)	Change in body weight (kg) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in BMI	Change in body mass index (BMI) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Participants Who Achieve (Yes/no): Body Weight Reduction =10%	Number of participants who achieved weight reduction =10% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	At week 68
Secondary	Participants Who Achieve (Yes/no): Body Weight Reduction =15%	Number of participants who achieved weight reduction =15% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	At week 68
Secondary	Participants Who Achieve (Yes/no): Body Weight Reduction =20%	Number of participants who achieved weight reduction =20% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	At week 68
Secondary	Change in HbA1c (%)	Change in glycated haemoglobin (HbA1c (%)) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in HbA1c (mmol/Mol)	Change in HbA1c (mmol/mol) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in FPG (mg/dL)	Change in fasting plasma glucose (FPG) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Fasting Serum Insulin	Change in fasting serum insulin from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol)	Number of participants who achieved HbA1c <7% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	At week 68
Secondary	Participants Who Achieve (Yes/no): HbA1c =6.5% (48 mmol/Mol)	Number of participants who achieved HbA1c =6.5% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	At week 68
Secondary	Participants Who Achieve (Yes/no): Body Weight Reduction =10% and HbA1c <7.0%	Number of participants who achieved weight reduction =10% of their baseline body weight and HbA1c <7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	At week 68
Secondary	Participants Who Achieve (Yes/no): Body Weight Reduction =15% and HbA1c <7.0%	Number of participants who achieved weight reduction =15% of their baseline body weight and HbA1c <7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	At week 68
Secondary	Change in Systolic Blood Pressure	Change in systolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Diastolic Blood Pressure	Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Total Cholesterol	Change in total cholesterol (measured in milligram per decilitre (mg/dL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in HDL Cholesterol	Change in high density lipoprotein (HDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in LDL Cholesterol	Change in low density lipoprotein (LDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in VLDL Cholesterol	Change in very low density lipoprotein (VLDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Free Fatty Acids	Change in free fatty acids (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Triglycerides	Change in triglycerides (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in hsCRP	Change in high sensitivity C-reactive protein (hsCRP; measured in milligram per ilitre (mg/L)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in PAI-1 Activity	Change in Plasminogen Activator Inhibitor-1 (PAI-1; measured in arbritary units per millilitre (AU/mL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Short Form 36 v2.0 Acute (SF-36) (Physical Functioning Score)	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured 8 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 'physical functioning domain'. The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on the data from in-trial observation period.	Baseline (week 0) to week 68
Secondary	Change in SF-36 (All Scores Except Physical Functioning)	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured 8 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, except physical functioning. The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on the data from in-trial observation period.	Baseline (week 0) to week 68
Secondary	Change in IWQOL-Lite for CT (Physical Function Domain (5-items) Score)	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 domain'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in IWQOL-Lite for CT (All Scores Except Physical Function)	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 and psychosocial domains, and for total'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score	The observed number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on two thresholds. The threshold of 4.3 is the default generic responder threshold defined in SF-36 manual for a general population. 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. Endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).	At week 68
Secondary	Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score	The observed number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on two different thresholds. The threshold of 20 was a preliminary responder threshold based on earlier studies. 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 the in-trial observation period which was defined as the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).	At week 68
Secondary	Number of TEAEs - Semaglutide 2.4 mg Versus Placebo	Adverse events (AEs) with onset during the on-treatment observation period were defined as treatment-emergent AEs (TEAEs). 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 seven consecutive missed doses.	Week 0 to week 75
Secondary	Number of SAEs - Semaglutide 2.4 mg Versus Placebo	Serious adverse event (SAE) results are based on the 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. Off-treatment time interval: time period with at least seven consecutive missed doses.	Week 0 to week 75
Secondary	Number of Treatment Emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemia Episodes - Semaglutide 2.4 mg Versus Placebo	Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period 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 7 consecutive missed doses. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG concentration. Blood glucose (BG) confirmed symptomatic hypoglycaemia: An episode that is BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.	Week 0 to week 75
Secondary	Change in Pulse - Semaglutide 2.4 mg Versus Placebo	Change in pulse from baseline (week 0) to week 68 is presented. Results are 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 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.	Baseline (week 0) to week 68
Secondary	Change in Amylase - Semaglutide 2.4 mg Versus Placebo	Change in amylase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are 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 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.	Baseline (week 0) to week 68
Secondary	Change in Lipase - Semaglutide 2.4 mg Versus Placebo	Change in lipase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are 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 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.	Baseline (week 0) to week 68
Secondary	Change in Calcitonin - Semaglutide 2.4 mg Versus Placebo	Change in calcitonin (nanogram/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are 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 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.	Baseline (week 0) to week 68