Primary outcome
What STEP 4 measured first
| Measure | Semaglutide 2.4 mgn=535 | Placebon=268 |
|---|---|---|
| In-trial | -8.3(8.1) | 6.5(7.7) |
| On-treatment | -8.8(7.8) | 6.1(7.7) |
Phase 3 · Semaglutide
STEP 4 trial results
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
- Participants
- 902
- Status
- completed
- Completed
- 2020-03-20
- Sponsor
- Novo Nordisk A/S
As posted on ClinicalTrials.gov (NCT03548987), updated at source Jan 19, 2022. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.
Side effects by arm
Side effects in STEP 4
Percent of participants affected, 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.. The most common events the registry lists.
| Event | Semaglutide: Run-in Period | Semaglutide 2.4: Treatment Period | Placebo: Treatment Period |
|---|---|---|---|
| Any serious event | 2.3% | 7.7% | 5.6% |
| Nausea | 46.8% | 14% | 4.9% |
| Diarrhoea | 23.5% | 14.4% | 7.1% |
| Constipation | 22.2% | 11.6% | 6% |
| Vomiting | 15.5% | 10.1% | 3% |
| Nasopharyngitis | 10.2% | 10.8% | 14.6% |
| Dyspepsia | 11.4% | 1.7% | 0.7% |
| Decreased appetite | 11.3% | 1.3% | 0% |
| Headache | 10.6% | 7.7% | 3.7% |
| Eructation | 7.9% | 2.6% | 0.4% |
| Abdominal pain | 7.4% | 6.4% | 3% |
| Fatigue | 7.4% | 4.9% | 2.2% |
| Influenza | 3.1% | 7.3% | 7.1% |
| Back pain | 2.9% | 5.2% | 6.7% |
| Gastrooesophageal reflux disease | 6.4% | 0.9% | 0.4% |
| Abdominal distension | 5.5% | 1.5% | 0.7% |
| Flatulence | 5.5% | 2.6% | 1.1% |
| Abdominal pain upper | 5.4% | 3.7% | 1.1% |
| Arthralgia | 2.3% | 4.7% | 5.2% |
Secondary outcomes
What else it measured
| Semaglutide 2.4 mgn=518 | Placebon=248 |
|---|---|
| -6.9(7.5) | 3.2(7.0) |
| Semaglutide 2.4 mgn=518 | Placebon=248 |
|---|---|
| 0(14) | 5(13) |
| Semaglutide 2.4 mgn=518 | Placebon=248 |
|---|---|
| 0(9) | 1(9) |
| Measure | Semaglutide 2.4 mgn=515 | Placebon=245 |
|---|---|---|
| Change in physical functioning score (SF-36) | 1.0(3.8) | -1.2(4.5) |
| Change in SF-36 role-physical score | 0.3(5.0) | -0.9(5.3) |
| Change in SF-36 bodily pain score | 0.5(7.0) | -1.5(7.7) |
| Change in SF-36 general health score | 0.3(5.2) | -1.8(5.8) |
| Change in SF-36 vitality score | 1.1(7.1) | -2.1(7.6) |
| Change in SF-36 social functioning score | 0.1(6.2) | -1.8(6.9) |
| Change in SF-36 mental health score | 0.2(6.2) | -2.2(7.6) |
| Change in SF-36 physical component summary | 0.8(4.9) | -0.9(5.6) |
| Change in SF-36 mental component summary | 0.0(6.2) | -2.4(8.5) |
| Change in SF-36 role-emotional score | 0.0(5.5) | -2.2(7.0) |
| Semaglutide 2.4 mgn=520 | Placebon=250 |
|---|---|
| -7.5(7.6) | 5.7(6.7) |
| Semaglutide 2.4 mgn=520 | Placebon=250 |
|---|---|
| -2.7(2.7) | 2.0(2.4) |
| Semaglutide 2.4 mgn=515 | Placebon=246 |
|---|---|
| -0.2(0.3) | 0.1(0.2) |
| Semaglutide 2.4 mgn=515 | Placebon=246 |
|---|---|
| -1.7(2.8) | 1.2(2.7) |
| Semaglutide 2.4 mgn=511 | Placebon=242 |
|---|---|
| -1.1(8.6) | 7.6(10.0) |
| Semaglutide 2.4 mgn=511 | Placebon=242 |
|---|---|
| -0.1(0.5) | 0.4(0.6) |
| Semaglutide 2.4 mgn=498 | Placebon=240 |
|---|---|
| 0.81(60.9) | 1.03(64.6) |
| Semaglutide 2.4 mgn=517 | Placebon=245 |
|---|---|
| 1.05(13.5) | 1.11(14.4) |
The trial
How STEP 4 was run
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.
- 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.
- 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.
Who could join the trial
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
Published papers
Papers from STEP 4
- 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.
- 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.
- 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.
- Wilkinson L, Holst-Hansen T, Laursen PN, Rinnov AR, Batterham RL, Garvey WT. Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity. Obesity (Silver Spring). 2023 Sep;31(9):2249-2259. doi: 10.1002/oby.23842.
- Kosiborod MN, Bhatta M, Davies M, Deanfield JE, Garvey WT, Khalid U, Kushner R, Rubino DM, Zeuthen N, Verma S. Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. Diabetes Obes Metab. 2023 Feb;25(2):468-478. doi: 10.1111/dom.14890. Epub 2022 Oct 28.
- 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.
Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.
GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.