Cited by 1,114Pharmacology and Obesity TreatmentDiabetes Treatment and ManagementBariatric Surgery and Outcomes

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index; 8 of the 24 sources its claims cite were checked for support.

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

Open access

Abstract

Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. Design, Setting, and Participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). Interventions: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. Main Outcomes and Measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. Conclusions and Relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03611582.

Overview

Integrity signals

Registry

Crossref · 10.1001/jama.2021.1831

Cites

34 of 34 references verified0 citation errors · 0 not checkable

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  • Probably not a substantial claim. 29
  • It may state two separate claims as one. 18
  • The quote only partly states this claim. 1
41 of 41
  • The authors state this as an assumption.

    All randomized participants remained receiving randomized treatment for the duration of the trial and did not receive rescue intervention.

    “The trial product estimand quantified the average treatment effect in all randomized participants, assuming they remained receiving randomized treatment for the duration of the trial (and without rescue intervention).”
  • The paper relies on this without support.

    The STEP 1 and STEP 3 trial populations and lifestyle interventions are sufficiently comparable to allow an indirect comparison of weight loss outcomes.

    “These findings suggest that the inclusion of intensive behavioral therapy plus an 8-week low-calorie diet ultimately may not contribute significant additional weight loss beyond that achieved by semaglutide and less-intensive lifestyle intervention.”
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Metadata

Authors
Wadden, T. A., Bailey, T. S., Billings, L. K., Davies, M., Frias, J. P., Koroleva, A., Lingvay, I., O’Neil, P. M., Rubino, D. M., Skovgaard, D., Wallenstein, S. O. R., Garvey, W. T., & STEP 3 Investigators
Affiliations
  • University of Pennsylvania (US)
  • AMCR Institute (US)
  • Endeavor Health (US)
  • University of Leicester (GB)
  • National Research Institute, Los Angeles, California
  • Novo Nordisk (Denmark) (DK)
  • The University of Texas Southwestern Medical Center (US)
  • Weight Management Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston
  • Washington Center for Weight Management and Research (US)
  • University of Alabama at Birmingham (US)
Corresponding author
Wadden, Thomas A.
Venue
JAMA
Published
2021-04-13
Volume
325
Issue
14
Pages
1403
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
OpenAlex
W3129305070
Cited by
1,114
References
33
Citations by year
2026: 237 · 2025: 287 · 2024: 222 · 2023: 147 · 2022: 132 · 2021: 85
FWCI
85.54
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079626)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
Keywords
semaglutide, obesity, overweight, weight loss, hypocaloric diet, GLP-1 receptor agonists, pharmacotherapy, adjunctive therapy, comorbid obesity, cardiometabolic risk factors, weight regain after weight loss
MeSH terms
Semaglutide, Adult, Combined Modality Therapy, Diet, Reducing, Double-Blind Method, Glucagon-Like Peptides, Female, Humans, Injections, Subcutaneous, Male, Middle Aged, Obesity, Weight Loss, Cognitive Behavioral Therapy, Anti-Obesity Agents, Overweight, Glucagon-Like Peptide 1

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