OverweightPhase 3STEP 3NCT03611582

Research Study to Look at How Well Semaglutide is at Lowering Weight When Taken Together With an Intensive Lifestyle Program

A Phase 3 study testing Semaglutide in people with Overweight and Obesity, run by Novo Nordisk A/S at 41 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Overweight, Obesity
What is being tested?: Semaglutide
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 611 participants
Where: 41 sitesUnited States
Study dates: 1 Aug 2018to 28 Apr 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female, age more than or equal to 18 years at the time of signing informed consent
Body mass index 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

Who cannot join

Hemoglobin A1c 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

Trial locations and contacts

41 sites in 1 country.

City, postcode or hospital

41 sites in 1 country

United States41 sites

Novo Nordisk Investigational Site
Albany, New York, 12203
Novo Nordisk Investigational Site
Anaheim, California, 92801
Novo Nordisk Investigational Site
Arlington, Virginia, 22206
Novo Nordisk Investigational Site
Austin, Texas, 78731
Novo Nordisk Investigational Site
Birmingham, Alabama, 35294
Novo Nordisk Investigational Site
Chapel Hill, North Carolina, 27517
Novo Nordisk Investigational Site
Charleston, South Carolina, 29425
Novo Nordisk Investigational Site
Chicago, Illinois, 60607
Novo Nordisk Investigational Site
Dallas, Texas, 75226
Novo Nordisk Investigational Site
Dallas, Texas, 75230
Novo Nordisk Investigational Site
Dallas, Texas, 75231
Novo Nordisk Investigational Site
Endwell, New York, 13760
Novo Nordisk Investigational Site
Escondido, California, 92025
Novo Nordisk Investigational Site
Evanston, Illinois, 60201-2477
Novo Nordisk Investigational Site
Fresno, California, 93720
Novo Nordisk Investigational Site
Fullerton, California, 92835
Novo Nordisk Investigational Site
Golden, Colorado, 80401
Novo Nordisk Investigational Site
Greensboro, North Carolina, 27408
Novo Nordisk Investigational Site
Hickory, North Carolina, 28601
Novo Nordisk Investigational Site
Honolulu, Hawaii, 96814
Novo Nordisk Investigational Site
Huntington Beach, California, 92648
Novo Nordisk Investigational Site
Kissimmee, Florida, 34744
Novo Nordisk Investigational Site
Knoxville, Tennessee, 37912
Novo Nordisk Investigational Site
Los Angeles, California, 90057
Novo Nordisk Investigational Site
Montgomery, Alabama, 36106
Novo Nordisk Investigational Site
Mt. Pleasant, South Carolina, 29464
Novo Nordisk Investigational Site
Newport News, Virginia, 23606
Novo Nordisk Investigational Site
Olympia, Washington, 98502
Novo Nordisk Investigational Site
Panama City, Florida, 32401
Novo Nordisk Investigational Site
Peoria, Arizona, 85381
Novo Nordisk Investigational Site
Philadelphia, Pennsylvania, 19104-3317
Novo Nordisk Investigational Site
Plantation, Florida, 33324
Novo Nordisk Investigational Site
Raleigh, North Carolina, 27609
Novo Nordisk Investigational Site
Rockwall, Texas, 75032
Novo Nordisk Investigational Site
Roswell, Georgia, 30076
Novo Nordisk Investigational Site
Round Rock, Texas, 78681
Novo Nordisk Investigational Site
Skokie, Illinois, 60077
Novo Nordisk Investigational Site
St. George, Utah, 84790
Novo Nordisk Investigational Site
Walnut Creek, California, 94598
Novo Nordisk Investigational Site
Wilmington, North Carolina, 28401
Novo Nordisk Investigational Site
Winchester, Virginia, 22601-3834

Other trials in United States

About this study

Official title: Effect and Safety of Semaglutide 2.4 mg Once-weekly as Adjunct to Intensive Behavioural Therapy in Subjects With Overweight or Obesity

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. Together with the medicine, the participant will also be part of an intensive lifestyle program where the participant will have talks with study staff about healthy food choices, what the participant can do to lose weight and be more physically active. The participant will either get semaglutide or "dummy" medicine - which treatment the participant gets is decided by chance. The participant 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. For the first 2 months the participant will be on a low calorie diet. The diet is made up of bars, shakes and 1 low calorie pre-prepared meal for each day. The study will last for about 1.5 years. The participant will have 32 clinic visits with the study doctor.

Conditions: Overweight, Obesity
Being tested: Semaglutide, Placebo (semaglutide)
Medical subject headings: Overweight, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SemaglutideDrug
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 (semaglutide)Drug
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.

Study groups in NCT03611582
Study group	Role	What they receive
Semaglutide	Experimental	Participants will receive semaglutide 2.4 mg during 68-week treatment period in addition to intensive behavioural therapy. Receives: Drug: Semaglutide
Semaglutide placebo	Placebo comparator	Participants will receive semaglutide placebo during 68-week treatment period in addition to intensive behavioural therapy. Receives: Drug: Placebo (semaglutide)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Body Weight (%)
Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment 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: 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).
Measured: Baseline (week 0) to week 68
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%
Number of participants who achieved greater than or equal to (≥) 5% weight loss after 68 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 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 randomization (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.
Measured: After 68 weeks

Secondary outcomes (29)

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%
Number of participants who achieved greater than or equal to (≥) 10% weight loss after 68 weeks 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Measured: After 68 weeks
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%
Number of participants who achieved greater than or equal to (≥) 15% weight loss after 68 weeks 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Measured: After 68 weeks
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%
Number of participants who achieved greater than or equal to (≥) 20% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 20% weight loss whereas 'No' infers number of participants who have not achieved ≥ 20% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Measured: After 68 weeks
Change in Waist Circumference
Change in waist circumference from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Systolic Blood Pressure
Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Short Form-36 (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 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 0 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Body Weight (Kg)
Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Body Mass Index
Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in HbA1c (%)
Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in HbA1c (mmol/Mol)
Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Fasting Plasma Glucose
Change in fasting plasma glucose 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Fasting Serum Insulin
Change in fasting serum insulin from week 0 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Diastolic Blood Pressure
Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Total Cholesterol
Change in fasting total cholesterol from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in High-density Lipoproteins (HDL)
Change in fasting HDL from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Low-density Lipoproteins (LDL)
Change in fasting LDL from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Very Low Density Lipoprotein (VLDL)
Change in fasting VLDL from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Free Fatty Acids
Change in fasting free fatty acids from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Triglycerides
Change in fasting triglycerides from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in High Sensitivity C-reactive Protein
Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
Change in Plasminogen Activator Inhibitor-1 Activity
Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 68
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 number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period which is uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
Measured: After 68 weeks
Change in Body Weight
Change in body weight from baseline (week 0) to week 8 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 randomisation (week 0) to last trial-related subject-site contact (week 75).
Measured: Baseline (week 0) to week 8
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. 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).
Measured: Baseline (week 0) 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 from week 0 to week 75 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).
Measured: Baseline (week 0) to week 75
Change in Pulse
Change in pulse from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period. 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).
Measured: Baseline (week 0) to week 68
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).
Measured: Baseline (week 0) 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).
Measured: Baseline (week 0) to week 68
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).
Measured: Baseline (week 0) to week 68

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Aug 201828 Apr 2020

First posted2 Aug 2018
Study start1 Aug 2018
Primary completion18 Mar 2020
Study completion28 Apr 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for OverweightStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 611 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03611582
Sponsor's protocol ID: NN9536-4375
Other IDs: U1111-1200-8199
Acronym: STEP 3
Status last verified: Nov 2021
First submitted: 17 Jul 2018
Last updated: 11 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

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.
PubMed 32441473
Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O'Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT; STEP 3 Investigators. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1403-1413. doi: 10.1001/jama.2021.1831.
PubMed 33625476
Wadden TA, Brown GK, Egebjerg C, Frenkel O, Goldman B, Kushner RF, McGowan B, Overvad M, Fink-Jensen A. Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials. JAMA Intern Med. 2024 Nov 1;184(11):1290-1300. doi: 10.1001/jamainternmed.2024.4346.
PubMed 39226070
Rubino D, Bjorner JB, Rathor N, Sharma AM, von Huth Smith L, Wharton S, Wadden T, Zeuthen N, Kolotkin RL. Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials. Diabetes Obes Metab. 2024 Jul;26(7):2945-2955. doi: 10.1111/dom.15620. Epub 2024 May 2.
PubMed 38698650
Heerspink HJL, Apperloo E, Davies M, Dicker D, Kandler K, Rosenstock J, Sorrig R, Lawson J, Zeuthen N, Cherney D. Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials. Diabetes Care. 2023 Apr 1;46(4):801-810. doi: 10.2337/dc22-1889.
PubMed 36801984
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.
PubMed 35724304
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.
PubMed 30122305

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect and Safety of Semaglutide 2.4 mg Once-weekly as Adjunct to Intensive Behavioural Therapy in Subjects With Overweight or Obesity
ClinicalTrials.gov ID: NCT03611582
Acronym / sponsor ID: STEP 3 / NN9536-4375
Conditions: Overweight, Obesity
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 611 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: 1 Aug 2018 (actual)
Primary completion: 18 Mar 2020 (actual)
Study completion: 28 Apr 2020 (actual)
First posted: 2 Aug 2018 (actual)
Results: Posted 9 Jul 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Semaglutide	Experimental	Drug: SemaglutideParticipants will receive semaglutide 2.4 mg during 68-week treatment period in addition to intensive behavioural therapy.
Semaglutide placebo	Placebo comparator	Drug: Placebo (semaglutide)Participants will receive semaglutide placebo during 68-week treatment period in addition to intensive behavioural therapy.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Male or female, age more than or equal to 18 years at the time of signing informed consent
Body mass index 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

Key exclusion criteria (2 listed)

Hemoglobin A1c 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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SemaglutideSubcutaneous (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.	Drug	Semaglutide
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.	Drug	Semaglutide placebo

Primary outcome

Change in Body Weight (%)
Time frame: Baseline (week 0) to week 68
Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment 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: 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).
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%
Time frame: After 68 weeks
Number of participants who achieved greater than or equal to (≥) 5% weight loss after 68 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 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 randomization (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.

29 secondary outcomes

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%
Time frame: After 68 weeks
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%
Time frame: After 68 weeks
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%
Time frame: After 68 weeks
Change in Waist Circumference
Time frame: Baseline (week 0) to week 68
Change in Systolic Blood Pressure
Time frame: Baseline (week 0) to week 68
Change in Short Form-36 (SF-36) - Physical Functioning Score
Time frame: Baseline (week 0) to week 68
Change in Body Weight (Kg)
Time frame: Baseline (week 0) to week 68
Change in Body Mass Index
Time frame: Baseline (week 0) to week 68
Change in HbA1c (%)
Time frame: Baseline (week 0) to week 68
Change in HbA1c (mmol/Mol)
Time frame: Baseline (week 0) to week 68
Change in Fasting Plasma Glucose
Time frame: Baseline (week 0) to week 68
Change in Fasting Serum Insulin
Time frame: Baseline (week 0) to week 68
Change in Diastolic Blood Pressure
Time frame: Baseline (week 0) to week 68
Change in Total Cholesterol
Time frame: Baseline (week 0) to week 68
Change in High-density Lipoproteins (HDL)
Time frame: Baseline (week 0) to week 68
Change in Low-density Lipoproteins (LDL)
Time frame: Baseline (week 0) to week 68
Change in Very Low Density Lipoprotein (VLDL)
Time frame: Baseline (week 0) to week 68
Change in Free Fatty Acids
Time frame: Baseline (week 0) to week 68
Change in Triglycerides
Time frame: Baseline (week 0) to week 68
Change in High Sensitivity C-reactive Protein
Time frame: Baseline (week 0) to week 68
Change in Plasminogen Activator Inhibitor-1 Activity
Time frame: Baseline (week 0) to week 68
Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
Time frame: After 68 weeks
Change in Body Weight
Time frame: Baseline (week 0) to week 8
Number of Treatment-emergent Adverse Events (AEs)
Time frame: Baseline (week 0) to week 75
Number of Serious Adverse Events (SAEs)
Time frame: Baseline (week 0) to week 75
Change in Pulse
Time frame: Baseline (week 0) to week 68
Change in Amylase
Time frame: Baseline (week 0) to week 68
Change in Lipase
Time frame: Baseline (week 0) to week 68
Change in Calcitonin
Time frame: Baseline (week 0) to week 68

Results and safety

Results posted to the registry on 9 Jul 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Semaglutide 2.4 mg	407	339
Placebo	204	166

Primary outcome: Change in Body Weight (%)

Time frame: Baseline (week 0) to week 68. Mean (Standard Deviation). Unit: Percentage

Measure	Semaglutide 2.4 mg n = 407	Placebo n = 204
In-trial observation period	-16.5 (10.1)	-5.8 (7.7)
On-treatment observation period	-17.6 (9.6)	-6.1 (7.6)

Semaglutide 2.4 mg vs Placebo: Treatment difference: -10.27 (95% CI -11.97 to -8.57), p <.0001, ANCOVA
Semaglutide 2.4 mg vs Placebo: Treatment difference: -12.67 (95% CI -14.34 to -11.00), p <0.0001, MMRM (mixed model repeated measurement)

Population analysed: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.

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

Time frame: After 68 weeks. Count of participants. Unit: Participants

Measure	Semaglutide 2.4 mg n = 407	Placebo n = 204
In-trial observation period: Yes	323	90
In-trial observation period: No	50	99
On-treatment observation period: Yes	300	82
On-treatment observation period: No	34	82

Semaglutide 2.4 mg vs Placebo: Odds Ratio (OR): 6.11 (95% CI 4.04 to 9.26), p <0.0001, Regression, Logistic
Semaglutide 2.4 mg vs Placebo: Odds Ratio (OR): 11.67 (95% CI 7.64 to 17.81), p <0.0001, MMRM (mixed model repeated measurement)

Population analysed: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.

29 secondary outcomes are reported in the full results.

Adverse events

Time frame: week 0 to week 75 Results are based on the SAS which included all participants who received at least one dose of semaglutide or placebo.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Semaglutide 2.4 mg	37 of 407 (9.1%)	379 of 407 (93.1%)	0 of 407
Placebo	6 of 204 (2.9%)	177 of 204 (86.8%)	0 of 204

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 32441473Kushner 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.
Results publication: PubMed 33625476Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O'Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT; STEP 3 Investigators. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1403-1413. doi: 10.1001/jama.2021.1831.
Derived from this study: PubMed 39226070Wadden TA, Brown GK, Egebjerg C, Frenkel O, Goldman B, Kushner RF, McGowan B, Overvad M, Fink-Jensen A. Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials. JAMA Intern Med. 2024 Nov 1;184(11):1290-1300. doi: 10.1001/jamainternmed.2024.4346.
Derived from this study: PubMed 38698650Rubino D, Bjorner JB, Rathor N, Sharma AM, von Huth Smith L, Wharton S, Wadden T, Zeuthen N, Kolotkin RL. Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials. Diabetes Obes Metab. 2024 Jul;26(7):2945-2955. doi: 10.1111/dom.15620. Epub 2024 May 2.
Derived from this study: PubMed 36801984Heerspink HJL, Apperloo E, Davies M, Dicker D, Kandler K, Rosenstock J, Sorrig R, Lawson J, Zeuthen N, Cherney D. Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials. Diabetes Care. 2023 Apr 1;46(4):801-810. doi: 10.2337/dc22-1889.
Derived from this study: PubMed 35724304Perreault 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.
Derived from this study: PubMed 30122305O'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.
Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Reporting Anchor and Disclosure (1452) study director

Novo Nordisk A/S

41 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Semaglutide in people with Overweight and Obesity, run by Novo Nordisk A/S at 41 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Body Weight (%) (time frame: Baseline (week 0) to week 68). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03611582, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2021.