Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity (STEP 4)

Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity Who Have Reached Target Dose During run-in Period

This study will look at the change in 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 medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what a participant can do to lose weight.

The participant will get semaglutide for the first 20 weeks. Then the participant will get either semaglutide or "dummy" medicine - which treatment the participant gets after the 20 weeks is decided by chance. The participants will need to take 1 injection 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.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolism and Nutrition Disorder
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 902
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg C, Denmark, 1958
    • Novo Nordisk Investigational Site
  • Køge, Denmark, 4600
    • Novo Nordisk Investigational Site
• Israel
  • Haifa, Israel, 35152
    • Novo Nordisk Investigational Site
  • Jerusalem, Israel, 91120
    • Novo Nordisk Investigational Site
  • Kfar Saba, Israel, 44281
    • Novo Nordisk Investigational Site
  • Petah-Tikva, Israel, 49372
    • Novo Nordisk Investigational Site
  • Tel Hashomer, Israel, 52621
    • Novo Nordisk Investigational Site
  • Tel-Aviv, Israel, 64239
    • Novo Nordisk Investigational Site
• Netherlands
  • Amsterdam, Netherlands, 1066 EC
    • Novo Nordisk Investigational Site
  • Amsterdam, Netherlands, 1105 AZ
    • Novo Nordisk Investigational Site
  • Arnhem, Netherlands, 6815 AD
    • Novo Nordisk Investigational Site
• Portugal
  • Braga, Portugal, 4710-243
    • Novo Nordisk Investigational Site
  • Coimbra, Portugal, 3000-561
    • Novo Nordisk Investigational Site
  • Matosinhos, Portugal, 4464-513
    • Novo Nordisk Investigational Site
  • Porto, Portugal, 4200-319
    • Novo Nordisk Investigational Site
  • Porto, Portugal, 4099-001
    • Novo Nordisk Investigational Site
  • Vila Nova de Gaia, Portugal, 4400-346
    • Novo Nordisk Investigational Site
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2001
      • Novo Nordisk Investigational Site
    • Johannesburg, Gauteng, South Africa, 2013
      • Novo Nordisk Investigational Site
    • Pretoria, Gauteng, South Africa, 0181
      • Novo Nordisk Investigational Site
    • Pretoria, Gauteng, South Africa, 0184
      • Novo Nordisk Investigational Site
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Novo Nordisk Investigational Site
  • North West
    • Brits, North West, South Africa, 0250
      • Novo Nordisk Investigational Site
• Spain
  • Almeria, Spain, 04009
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28009
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28040
    • Novo Nordisk Investigational Site
  • Sabadell, Spain, 08208
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41013
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41003
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41009
    • Novo Nordisk Investigational Site
• Sweden
  • Malmö, Sweden, 205 02
    • Novo Nordisk Investigational Site
  • Stockholm, Sweden, 141 86
    • Novo Nordisk Investigational Site
  • Uppsala, Sweden, 751 85
    • Novo Nordisk Investigational Site
• Switzerland
  • Genève 14, Switzerland, 1211
    • Novo Nordisk Investigational Site
  • Olten, Switzerland, 4600
    • Novo Nordisk Investigational Site
  • St. Gallen, Switzerland, 9007
    • Novo Nordisk Investigational Site
  • St. Gallen, Switzerland, 9016
    • Novo Nordisk Investigational Site
  • Zollikerberg, Switzerland, 8125
    • Novo Nordisk Investigational Site
  • Zürich, Switzerland, 8091
    • Novo Nordisk Investigational Site
• Ukraine
  • Kharkiv, Ukraine, 61039
    • Novo Nordisk Investigational Site
  • Kyiv, Ukraine, 04114
    • Novo Nordisk Investigational Site
  • Kyiv, Ukraine, 03039
    • Novo Nordisk Investigational Site
  • Kyiv, Ukraine, 04050
    • Novo Nordisk Investigational Site
  • Odesa, Ukraine, 65059
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Novo Nordisk Investigational Site
  • California
    • Fresno, California, United States, 93720
      • Novo Nordisk Investigational Site
    • San Diego, California, United States, 92108
      • Novo Nordisk Investigational Site
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Novo Nordisk Investigational Site
    • Roswell, Georgia, United States, 30076
      • Novo Nordisk Investigational Site
    • Suwanee, Georgia, United States, 30024
      • Novo Nordisk Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Novo Nordisk Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Novo Nordisk Investigational Site
  • Maryland
    • Elkridge, Maryland, United States, 21075-6437
      • Novo Nordisk Investigational Site
  • Michigan
    • Buckley, Michigan, United States, 49620
      • Novo Nordisk Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198-3020
      • Novo Nordisk Investigational Site
  • New York
    • New York, New York, United States, 10016
      • Novo Nordisk Investigational Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Novo Nordisk Investigational Site
    • Greenville, North Carolina, United States, 27834
      • Novo Nordisk Investigational Site
    • Raleigh, North Carolina, United States, 27612
      • Novo Nordisk Investigational Site
    • Salisbury, North Carolina, United States, 28144
      • Novo Nordisk Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Novo Nordisk Investigational Site
    • Dayton, Ohio, United States, 45406
      • Novo Nordisk Investigational Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620-7352
      • Novo Nordisk Investigational Site
    • Bristol, Tennessee, United States, 37620
      • Novo Nordisk Investigational Site
    • Chattanooga, Tennessee, United States, 37404
      • Novo Nordisk Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75226
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75231
      • Novo Nordisk Investigational Site
  • Virginia
    • Arlington, Virginia, United States, 22206
      • Novo Nordisk Investigational Site
    • Richmond, Virginia, United States, 23226
      • Novo Nordisk Investigational Site
  • Washington
    • Wenatchee, Washington, United States, 98801-2028
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent
• Body mass index greater than or equal to 30 kg/sqm or greater than or equal to 27 kg/sqm with the presence of at least one of the following weight related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease
• History of at least one self-reported unsuccessful dietary effort to lose body weight

Exclusion Criteria:

• Haemoglobin A1c greater than or equal to 48 mmol/mol (6.5%) as measured by central laboratory at screening
• A self-reported change in body weight more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide; Run-in Period: Participants will receive semaglutide at an escalating doses (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg) for 20 weeks (week 0 to week 20). The dose will be escalated to next level every 4 weeks. Maintenance period: Participants will be randomized to receive semaglutide injection for 48 weeks (from week 20 to week 68). The trial product will be administered as an adjunct to a reduced-calorie diet and increased physical activity during the trial period.	Drug: Semaglutide; Subcutaneous (under the skin) injection of semaglutide once-weekly.
Placebo Comparator: Placebo; Run-in Period: Participants will receive semaglutide at an escalating doses (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg) for 20 weeks (week 0 to week 20). The dose will be escalated to next level every 4 weeks. Maintenance period: Participants will be randomized to receive semaglutide placebo injection for 48 weeks (from week 20 to week 68). The trial product will be administered as an adjunct to a reduced-calorie diet and increased physical activity during the trial period.	Drug: Semaglutide; Subcutaneous (under the skin) injection of semaglutide once-weekly.; Drug: Placebo; Subcutaneous (under the skin) injection of semaglutide placebo once-weekly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Randomisation to Week 68 in Body Weight (%)	Change in body weight from baseline (week 20) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Waist Circumference	Change in waist circumference from baseline (week 20) 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Systolic Blood Pressure	Change in systolic blood pressure from week 20 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Diastolic Blood Pressure	Change in diastolic blood pressure from week 20 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Physical Functioning Score (Short Form 36 [SF-36])	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 eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). 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 20 in the 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 the data from in-trial observation period which is the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Body Weight [Kilogram (Kg)]	Change in body weight from week 20 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomisation (week 20) to week 68
Change in Body Mass Index (BMI)	Change in BMI from week 20 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Haemoglobin A1c (HbA1c) [%]	Change in HbA1c from week 20 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in HbA1c [Millimoles Per Mole (mmol/Mol)]	Change in HbA1c from week 20 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]	Change in fasting plasma glucose from week 20 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]	Change in fasting plasma glucose from week 20 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Fasting Serum Insulin	Change in fasting serum insulin from baseline (week 20) to week 68 [measured as milli-international units per milliliter (mIU/mL)] 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Total Cholesterol	Change in fasting total cholesterol from baseline (week 20) to week 68 (measured as mmol/L) 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in High-density Lipoproteins (HDL)	Change in fasting HDL from baseline (week 20) to week 68 (measured as mmol/L) 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Low-density Lipoproteins (LDL)	Change in fasting LDL from baseline (week 20) to week 68 (measured as mmol/L) 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Very Low-density Lipoproteins (VLDL)	Change in fasting VLDL from baseline (week 20) to week 68 (measured as mmol/L) 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Free Fatty Acids	Change in fasting free fatty acids from baseline (week 20) to week 68 (measured as mmol/L) 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Change in Triglycerides	Change in fasting triglycerides from baseline (week 20) to week 68 (measured as mmol/L) 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score	The number of participants achieving at least a 4.3-point increase in SF-36 physical functioning score from baseline (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved 4.3 points of increase of the score and 'No' infers number of participants who have not achieved 4.3 points of increase of the score. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomisation (week 20) to week 68
Subjects Who Gain Weight (Yes/no)	The number of participants with weight gain from the start of the randomised period (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have gained weight and 'No' infers number of participants who have not gained weight. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomisation (week 20) to week 68
Change in Body Weight	The body weight change (%) from 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction < 0%	The number of participants who achieved less than (<) 0% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved <0% weight loss whereas 'No' infers number of participants who have not achieved <0% weight loss.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5%	The number of participants who achieved greater than or equal to (≥) 5% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 5% weight loss whereas 'No' infers number of participants who have not achieved ≥ 5% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10%	The number of participants who achieved ≥ 10% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 10% weight loss whereas 'No' infers 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15%	The number of participants who achieved ≥ 15% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 15% weight loss whereas 'No' infers 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 start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Number of Treatment-emergent Adverse Events (AEs)	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 that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 0-20 run-in period). The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomisation (week 20)
Number of Treatment-emergent AEs	An 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 TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 20-75). The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 75
Number of Serious Adverse Events (SAEs)	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. The SAEs occurred during run-in period from week 0 to week 20 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomisation (week 20)
Number of Serious Adverse Events (SAEs)	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. The SAEs occurred during run-in period from week 0 to week 20 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 75
Change in Pulse	Change in pulse rate from week 0 week to week 20 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomisation (week 20)
Change in Pulse	Change in pulse from week 20 and 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period.On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68
Change in Amylase	Change in amylase (measured as units per liter [U/L]) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Run-in (week) 0 to randomization (week 20)
Change in Amylase	Change in amylase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68
Change in Lipase	Change in lipase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomization (week 20)
Change in Lipase	Change in lipase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68
Change in Calcitonin	Change in calcitonin (measured as nanogram per liter (ng/L)]) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomization (week 20)
Change in Calcitonin	Change in calcitonin (measured as ng/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• 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.
• Perreault L, Davies M, Frias JP, Laursen PN, Lingvay I, Machineni S, Varbo A, Wilding JPH, Wallenstein SOR, le Roux CW. Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program. Diabetes Care. 2022 Oct 1;45(10):2396-2405. doi: 10.2337/dc21-1785.
• O'Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, Carson CG, Jepsen CH, Kabisch M, Wilding JPH. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. Epub 2018 Aug 16.
• Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D; STEP 4 Investigators. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1414-1425. doi: 10.1001/jama.2021.3224.
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Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2018
• Primary Completion (Actual): February 22, 2020
• Study Completion (Actual): March 20, 2020

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: May 25, 2018
• First Posted (Actual): June 7, 2018

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Body Weight; Obesity; Overweight; Nutrition Disorders
• Other Study ID Numbers: NN9536-4376; U1111-1201-0898 (Other Identifier: World Health Organization (WHO)); 2017-003473-34 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No