Weight regain following discontinuation of glucagon-like peptide-1 receptor agonists in adults who are overweight or obese: a systematic review and meta-analysis
- Design
- Meta-analysis · 8993 participants · Unknown outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Synthesis of studies conducted predominantly in people with obesity/overweight.
- Could weight loss explain it?
- Unknown[Auto] Harm signal; weight-loss mediation not the relevant question, but consider whether harms relate to rapid weight loss or reduced intake.
- Study tier
- Study tier 2[Auto] Systematic review/meta-analysis of randomized trials (auto-provisional; heterogeneity and included-study quality not assessed).
- Assessment
- Version 1 · automatic, not yet reviewed by a person · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
[Auto, unreviewed; quoted from abstract conclusions] There is a significant weight rebound phenomenon after discontinuation of GLP-1RAs, and the rebound magnitudes vary among different types of drugs. At the same time, there is a risk of adverse reactions during the use of such drugs.
01Findings
What the study reported
- Drugs
- Semaglutide, Liraglutide, Dulaglutide, Tirzepatide
- Comparator
- the continued treatment group
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Sample size
- 8993
Study quality details
- Study design
- Meta-analysis
- Sample size
- 8993
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- not stated
- Follow up duration
- not stated
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% confidence interval (CI
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- The authors declare there are no competing interests.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[OBJECTIVE] This study aims to explore the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on weight changes and the occurrence of adverse reactions in overweight or obese adults after drug withdrawal. [METHODS] Computerized searches were conducted in evidence-based databases such as PubMed, Embase, Cochrane Library and Scopus. The search period was from the establishment of the database to December 2025. Collect randomised controlled trials (RCTs) and controlled trials on GLP-1RAs, including tirzepatide, semaglutide, liraglutide, and dulaglutide, for the treatment of overweight or obese adult patients. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias V2.0 tool provided by the Cochrane Collaboration, and meta-analysis was performed using the R programming language. [RESULTS] A total of 699 studies were initially retrieved. Eventually, six studies involving 8,993 patients were included in the quantitative analysis, comprising 5,553 patients in the discontinuation group and 3,440 in the continued treatment group. The results of the meta-analysis showed that, compared with the continued treatment group, the weight difference in the discontinuation group was mean difference (MD) = 17.90%, 95% confidence interval (CI) [14.11-21.69], P < 0.0001. It can be seen that there was a significant rebound in weight after drug withdrawal, and there was statistical heterogeneity among the studies (P = 0.0082). Subgroup analysis further revealed that the weight rebound amplitude after discontinuation of tirzepatide was significantly higher than that of semaglutide. This result suggests that the differences in the mechanism of action of different GLP-1RAs may be the reason for the differences in weight changes after discontinuation. In addition, the percentage difference in body weight between after and before drug withdrawal was MD = 9.11%, 95% CI [7.91-10.30], P < 0.0001, further verifying the trend of weight rebound after drug withdrawal. The summary of adverse reaction reports analyzed and studied indicates that after drug withdrawal, the overall adverse reactions of patients decreased, gastrointestinal adverse reactions decreased, and the incidence of cardiovascular events was not affected by drug withdrawal. [CONCLUSION] There is a significant weight rebound phenomenon after discontinuation of GLP-1RAs, and the rebound magnitudes vary among different types of drugs. At the same time, there is a risk of adverse reactions during the use of such drugs.