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Cited by 7Pharmacology and Obesity TreatmentDiabetes Treatment and ManagementBariatric Surgery and Outcomes

Rebound or Retention: A Meta-Analysis of Weight Regain After the Discontinuation of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Other Anti-Obesity Drugs

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Kolli, Ravi Teja, Aoutla, Sridevi, Jyothi, Nirmal, Mohamed Kalifa, Mohamed Raghib Hussain, Raju, Arvin, Cheenikkal Muralidharan, Kavya·2025·Cureus
DOI 10.7759/cureus.94926PMC PMC12535773
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Abstract

Anti-obesity pharmacotherapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists and orlistat, are effective for weight loss; however, weight regain following treatment discontinuation remains a major concern. This meta-analysis aimed to quantify the magnitude of weight regain after reaching peak weight loss, and to compare rebound effects across four commonly used agents: semaglutide, liraglutide, exenatide, and orlistat. A systematic search was conducted in PubMed (n = 498), Cochrane Library (n = 41), Scopus (n = 258), ScienceDirect (n = 248), and Web of Science (n = 158) from January 2010 to October 2024. After removing 153 duplicates, 950 records were screened. Following full-text assessment, 36 studies were included in the final analysis. Data extraction was performed using Excel (Microsoft® Corp., Redmond, WA, USA), and graphical data were digitized using WebPlotDigitizer. Risk of bias was assessed using RoB 2.0, and meta-analyses were conducted with Comprehensive Meta-Analysis (v3.7), using mean difference (MD) and 95% confidence intervals (CI). I² statistics were used to assess heterogeneity, and Egger's and Begg's tests were used to evaluate publication bias. Semaglutide showed the highest weight regain after discontinuation (MD = -5.15 kg; 95% CI: -5.27 to -5.03), followed by exenatide (MD = -3.06 kg; 95% CI: -3.91 to -2.22), liraglutide (MD = -1.50 kg; 95% CI: -2.41 to -0.26), and orlistat (MD = -1.66 kg; 95% CI: -2.75 to -0.58). Heterogeneity was moderate to high (I² ranging from 41.7% to 99.7%). Egger's test showed significant bias for liraglutide (p = 0.013), while no major bias was found for the other agents. This meta-analysis demonstrates that weight regain is common and drug-dependent following the discontinuation of anti-obesity pharmacotherapies. The findings emphasize the need for sustained, long-term treatment strategies to maintain weight loss and to manage obesity as a chronic disease.

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  • The abrupt resurgence of intrusive food-related cognitions upon a missed dose or discontinuation can be profoundly distressing, frequently precipitating rapid weight regain and a sense of treatment failure.

    “Consequently, the abrupt resurgence of intrusive food-related cognitions upon a missed dose or discontinuation can be profoundly distressing, frequently precipitating rapid weight regain and a sense of treatment failure [61,62].”

    From Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support—A Narrative Review (2026) · cites this paper as [62]

    The Review discussion reports substantial weight regain within a few months after stopping treatment. It does not establish that a missed dose causes intrusive food-related thoughts, or that those thoughts precipitate weight regain, distress, or a perceived sense of treatment failure. The Conclusions instead characterize regain as a predictable biological response, not a treatment failure. No page numbers are available in our copy. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Kolli, R. T., Aoutla, S., Jyothi, N., Mohamed Kalifa, M. R. H., Raju, A., & Cheenikkal Muralidharan, K.
Affiliations
  • Worthing Hospital (GB)
  • Max Healthcare (IN)
Venue
Cureus
Publisher
Springer Science and Business Media LLC
Published
2025-10-19
Volume
17
Issue
10
Pages
e94926-e94926
ISSN
2168-8184 (ISSN-L)
DOI
10.7759/cureus.94926
PMC
PMC12535773
OpenAlex
W4415342721
Cited by
7
References
17
Citations by year
2026: 7
FWCI
0.95
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cureus (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
Keywords
weight regain, GLP-1 receptor agonists, semaglutide, liraglutide, exenatide, orlistat, anti-obesity drugs, weight loss maintenance, obesity pharmacotherapy, weight retention, publication bias, risk of bias assessment, effect size heterogeneity

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