Two-year Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity (STEP 5)

Two-year Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity

This study will look at the change in body weight from the start to the end of the study. Researchers will compare the weight loss in people taking semaglutide (a new medicine) to people taking "dummy" medicine. In addition to taking the medicine, participants will also have talks with study staff about healthy food choices, how the participant can be more physically active and what participants can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment the participant gets is decided by chance. 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 2 years. The participants will have 19 clinic visits and 15 phone calls with the study doctor.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo (Semaglutide)

• Study Type: Interventional
• Enrollment (Actual): 304
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G2
    • Novo Nordisk Investigational Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3Z 2N6
      • Novo Nordisk Investigational Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
      • Novo Nordisk Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Novo Nordisk Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8L 5G8
      • Novo Nordisk Investigational Site
    • Hamilton, Ontario, Canada, L8M 1K7
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M4P 1P2
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M4G 3E8
      • Novo Nordisk Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H4N 2W2
      • Novo Nordisk Investigational Site
• Hungary
  • Budapest, Hungary, H-1134
    • Novo Nordisk Investigational Site
  • Budapest, Hungary, 1132
    • Novo Nordisk Investigational Site
  • Budapest, Hungary, 1152
    • Novo Nordisk Investigational Site
  • Debrecen, Hungary, 4043
    • Novo Nordisk Investigational Site
  • Komarom, Hungary, 2900
    • Novo Nordisk Investigational Site
  • Szekszárd, Hungary, 7100
    • Novo Nordisk Investigational Site
• Italy
  • Bologna, Italy, 40138
    • Novo Nordisk Investigational Site
  • Palermo, Italy, 90127
    • Novo Nordisk Investigational Site
  • Pisa, Italy, 56124
    • Novo Nordisk Investigational Site
  • Rome, Italy, 00168
    • Novo Nordisk Investigational Site
  • Siena, Italy, 53100
    • Novo Nordisk Investigational Site
• Spain
  • Alcorcón, Spain, 28922
    • Novo Nordisk Investigational Site
  • Almeria, Spain, 04009
    • Novo Nordisk Investigational Site
  • Hospitalet de Llobregat, Spain, 08907
    • Novo Nordisk Investigational Site
  • Pamplona, Spain, 31008
    • Novo Nordisk Investigational Site
  • Pozuelo de Alarcon, Spain, 28223
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41010
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35222
      • Novo Nordisk Investigational Site
  • California
    • Los Angeles, California, United States, 90057
      • Novo Nordisk Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novo Nordisk Investigational Site
    • Golden, Colorado, United States, 80401
      • Novo Nordisk Investigational Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Novo Nordisk Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32205
      • Novo Nordisk Investigational Site
    • Ocala, Florida, United States, 34471
      • Novo Nordisk Investigational Site
  • Missouri
    • Saint Peters, Missouri, United States, 63303
      • Novo Nordisk Investigational Site
  • Montana
    • Butte, Montana, United States, 59701
      • Novo Nordisk Investigational Site
  • New York
    • Albany, New York, United States, 12203
      • Novo Nordisk Investigational Site
    • Rochester, New York, United States, 14609
      • Novo Nordisk Investigational Site
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Novo Nordisk Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Round Rock, Texas, United States, 78681
      • Novo Nordisk Investigational Site
  • Virginia
    • Arlington, Virginia, United States, 22206
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, age more than or equal to 18 years at the time of signing informed consent
• Body mass index (BMI) more than or equal to 30 kg/m^2 or more than or equal to 27 kg/m^2 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:

• HbA1c more than or equal to 48 mmol/mol (6.5%) as measured by the 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; Participants will receive semaglutide 2.4 mg during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity.	Drug: Semaglutide; Subcutaneous (s.c., under the skin) injections of semaglutide once weekly at escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks
Placebo Comparator: Placebo; Participants will receive placebo (semaglutide) during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity.	Drug: Placebo (Semaglutide); S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline (Week 0) to Week 104 in Body Weight	Percentage change in body weight for both in-trial and on-treatment observation period from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).	From Baseline (Week 0) to Week 104
Number of Participants Who Achieved (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 104 weeks 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. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).	At Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%	Number of participants who achieved >=10% weight loss at 104 weeks 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 outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	At Week 104
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%	Number of participants who achieved >=15% weight loss at 104 weeks 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 outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	At Week 104
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%	Number of participants who achieved >=20% weight loss at 104 weeks 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 outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	At Week 104
Change From Baseline (Week 0) to Week 104 in Waist Circumference	Change in waist circumference from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Body Weight (kg)	Change in body weight from baseline (week 0) to week 104 in kilogram (kg) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Body Mass Index (BMI)	Change in BMI from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Systolic Blood Pressure	Change in systolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Diastolic Blood Pressure	Change in diastolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in Total Cholesterol-ratio to Baseline	Change in total cholesterol from baseline (week 0) to week 104 measured in milligrams per deciliter (mg/dL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in High Density Lipoprotein (HDL) Cholesterol-ratio to Baseline	Change in HDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in Low Density Lipoprotein (LDL) Cholesterol-ratio to Baseline	Change in LDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in Very Low Density Lipoprotein (VLDL) Cholesterol-ratio to Baseline	Change in VLDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in Free Fatty Acids-ratio to Baseline	Change in free fatty acids from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in Triglycerides-ratio to Baseline	Change in triglycerides from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline	Change in hsCRP from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in Glycated Haemoglobin (HbA1c) (Percent [%])	Change in HbA1c from baseline (week 0) to week 104 in % is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in HbA1c (mmol/Mol)	Change in HbA1c from baseline (week 0) to week 104 in millimole per mole (mmol/mol) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Fasting Plasma Glucose (FPG) (mmol/L)	Change in FPG from baseline (week 0) to week 104 in millimoles per liter (mmol/L) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in FPG (mg/dL)	Change in FPG from baseline (week 0) to week 104 in mg/dL is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in Fasting Serum Insulin-ratio to Baseline (Pmol/L)	Change in fasting serum insulin from baseline (week 0) to week 104 measured in picomole per liter (pmol) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Change in Fasting Serum Insulin-ratio to Baseline (mIU/mL)	Change in fasting serum insulin from baseline (week 0) to week 104 measured in milli-international units per milliliter (mIU/mL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Percentage Change From Baseline (Week 0) to Week 52 in Body Weight	Percentage change in body weight from baseline (week 0) to week 52 is presented.	From Baseline (Week 0) to Week 52
Change From Baseline (Week 0) to Week 52 in Body Weight (kg)	Change in body weight from baseline (week 0) to week 52 in kg is presented.	From Baseline (Week 0) to Week 52
Change From Baseline (Week 0) to Week 52 in Body Mass Index (BMI)	Change in BMI from baseline (week 0) to week 52 is presented.	From Baseline (Week 0) to Week 52
Change From Baseline (Week 0) to Week 52 in Waist Circumference	Change in waist circumference from baseline (week 0) to week 52 is presented.	From Baseline (Week 0) to Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%	Number of participants who achieved >=5% weight loss at 52 weeks 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.	At Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%	Number of participants who achieved >=10% weight loss at 52 weeks 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.	At Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%	Number of participants who achieved >=15% weight loss at 52 weeks 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.	At Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%	Number of participants who achieved >=20% weight loss at 52 weeks 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.	At Week 52
Number of Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).	From Baseline (Week 0) to Week 111
Number of Serious Adverse Events (SAEs)	A SAE was 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 from week 0 to week 111 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).	From Baseline (Week 0) to Week 111
Change From Baseline (Week 0) to Week 104 in Pulse	Change in pulse from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Amylase	Change in amylase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Lipase	Change in lipase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).	From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Calcitonin	Change in calcitonin from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).	From Baseline (Week 0) to Week 104

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Reporting Anchor and Disclosure (1452), 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.
• Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jodar E, Kandler K, Rigas G, Wadden TA, Wharton S; STEP 5 Study Group. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022 Oct;28(10):2083-2091. doi: 10.1038/s41591-022-02026-4. Epub 2022 Oct 10.
• Wharton S, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jodar E, Kandler K, Rigas G, Wadden TA, Garvey WT. Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5. Obesity (Silver Spring). 2023 Mar;31(3):703-715. doi: 10.1002/oby.23673. Epub 2023 Jan 18.

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2018
• Primary Completion (Actual): January 29, 2021
• Study Completion (Actual): March 23, 2021

Study Registration Dates

• First Submitted: October 1, 2018
• First Submitted That Met QC Criteria: October 1, 2018
• First Posted (Actual): October 3, 2018

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Obesity; Overweight
• Other Study ID Numbers: NN9536-4378; 2017-003726-32 (Registry Identifier: European Medicines Agency (EudraCT)); U1111-1202-1740 (Other Identifier: World Health Organization (WHO))

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