Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial
- PMID: 33755728
- PMCID: PMC7988425
- DOI: 10.1001/jama.2021.3224
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial
Abstract
Importance: The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown.
Objective: To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly.
Design, setting, and participants: Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes.
Interventions: A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups.
Main outcomes and measures: The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]).
Results: Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%).
Conclusions and relevance: Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks.
Trial registration: ClinicalTrials.gov Identifier: NCT03548987.
Conflict of interest statement
Figures
![Figure 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7988425/bin/jama-e213224-g001.gif)
![Figure 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7988425/bin/jama-e213224-g002.gif)
Comment in
-
In adults with overweight or obesity, continued weekly semaglutide after a 20-wk run-in improved weight loss.Ann Intern Med. 2021 Aug;174(8):JC88. doi: 10.7326/ACPJ202108170-088. Epub 2021 Aug 3. Ann Intern Med. 2021. PMID: 34339232
Similar articles
-
Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Am J Cardiol. 2024 Jul 1;222:121-130. doi: 10.1016/j.amjcard.2024.04.041. Epub 2024 Apr 26. Am J Cardiol. 2024. PMID: 38679221 Review.
-
Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.JAMA. 2022 Jan 11;327(2):138-150. doi: 10.1001/jama.2021.23619. JAMA. 2022. PMID: 35015037 Free PMC article. Clinical Trial.
-
Clinical review of subcutaneous semaglutide for obesity.J Clin Pharm Ther. 2022 Feb;47(2):184-193. doi: 10.1111/jcpt.13574. Epub 2021 Dec 28. J Clin Pharm Ther. 2022. PMID: 34964141 Review.
-
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. JAMA. 2021. PMID: 33625476 Free PMC article. Clinical Trial.
-
Once-Weekly Semaglutide in Adults with Overweight or Obesity.N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10. N Engl J Med. 2021. PMID: 33567185 Clinical Trial.
Cited by
-
Balancing innovation and affordability in anti-obesity medications: the role of an alternative weight-maintenance program.Health Aff Sch. 2024 May 2;2(6):qxae055. doi: 10.1093/haschl/qxae055. eCollection 2024 Jun. Health Aff Sch. 2024. PMID: 38828004 Free PMC article.
-
A Real-World Study of the Effectiveness and Safety of Semaglutide for Weight Loss.Cureus. 2024 May 2;16(5):e59558. doi: 10.7759/cureus.59558. eCollection 2024 May. Cureus. 2024. PMID: 38826889 Free PMC article.
-
Interaction of Semaglutide and Ziprasidone in a Patient With Schizophrenia: A Case Report.Cureus. 2024 Apr 29;16(4):e59319. doi: 10.7759/cureus.59319. eCollection 2024 Apr. Cureus. 2024. PMID: 38817502 Free PMC article.
-
Nutritional Considerations During Major Weight Loss Therapy: Focus on Optimal Protein and a Low-Carbohydrate Dietary Pattern.Curr Nutr Rep. 2024 May 30. doi: 10.1007/s13668-024-00548-6. Online ahead of print. Curr Nutr Rep. 2024. PMID: 38814519 Review.
-
Therapeutic targeting of white adipose tissue metabolic dysfunction in obesity: mechanisms and opportunities.MedComm (2020). 2024 May 24;5(6):e560. doi: 10.1002/mco2.560. eCollection 2024 Jun. MedComm (2020). 2024. PMID: 38812572 Free PMC article. Review.
References
-
- Garvey WT, Mechanick JI, Brett EM, et al. ; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines . American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22(suppl 3):1-203. doi:10.4158/EP161365.GL - DOI - PubMed
Publication types
MeSH terms
Substances
Associated data
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical