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Weight regain after cessation of medication for weight management: systematic review and meta-analysis

Abstract:
Objectives: To quantify and compare the rate of weight regain after cessation of weight management medications (WMMs) in adults with overweight or obesity. Design: Systematic review and meta-analysis. Study selection: Trial registries and databases (Medline, Embase, PsycINFO, CINAHL, Cochrane, Web of Science, and trial registries) were searched from inception until February 2025 for randomised controlled trials (RCTs), non-randomised trials, and observational studies that included WMM (≥8 weeks) with follow-up for ≥4 weeks after cessation of treatment in adults with overweight or obesity. Comparators were any non-drug weight loss intervention or placebo. Data extraction and synthesis: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Two independent reviewers screened titles, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias 2 tool for RCTs and the ROBINS-I tool for non-randomised trials. Data were analysed using mixed effect, meta-regression, and time-to-event models. Weight regain after cessation of WMM was compared with that reported after cessation of behavioural weight management programmes (BWMPs). Main outcome measures: The primary outcome was rate of weight regain from end of treatment, with associated changes in cardiometabolic markers as a secondary outcome. Results: Of the 9288 titles screened, 37 studies (63 intervention arms, 9341 participants) were included. Average treatment duration was 39 (range 11-176) weeks, with average follow-up of 32 (4-104) weeks. The average monthly rate of weight regain was 0.4 kg (95% confidence interval (CI) 0.3 to 0.5) (mixed model 0.3 kg (0.2 to 0.4) monthly v control in RCTs). All cardiometabolic markers were projected to return to baseline within 1.4 years after the cessation of WMM. Weight regain was faster after WMM than after BWMP (by 0.3 kg (0.22 to 0.34) monthly), independent of initial weight loss. Estimates and precision were robust in sensitivity analyses. Conclusions: This review found that cessation of WMM is followed by rapid weight regain and reversal of beneficial effects on cardiometabolic markers. Regain after WMM was faster than after BWMP. These findings suggest caution in short term use of these drugs without a more comprehensive approach to weight management. Systematic review registration: PROSPERO CRD42024532069.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1136/bmj-2025-085304

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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0002-5432-863X
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Institution:
University of Oxford
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Institution:
University of Oxford
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Institution:
University of Oxford
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Institution:
University of Oxford
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Author


Publisher:
British Medical Journal Publishing Group
Journal:
BMJ More from this journal
Volume:
392
Pages:
e085304
Article number:
e085304
Publication date:
2026-01-07
Acceptance date:
2025-11-06
DOI:
EISSN:
1756-1833
ISSN:
1756-1833
Pmid:
41500720


Language:
English
Pubs id:
2349332
UUID:
uuid_e4aafdcc-9708-4882-a03b-4627f41fc3a6
Local pid:
pubs:2349332
Source identifiers:
3646601
Deposit date:
2026-01-09
ARK identifier:
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