Metabolic rebound after GLP-1 receptor agonist discontinuation: a systematic review and meta-analysis
Abstract
Summary Background To quantify the extent of metabolic and cardiovascular rebound following the discontinuation of GLP-1 receptor agonist (GLP-1RA) therapy in adults with obesity, type 2 diabetes, or type 1 diabetes, and identify potential modifiers of these outcomes. Methods We conducted a systematic review and meta-analysis of randomized controlled trials including adults and adolescents treated with GLP-1RAs, followed by a post-discontinuation follow-up of at least 12 weeks. Databases searched included MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov, with no language restrictions, and published up to October 17, 2025. We assessed changes in anthropometric, glycemic, cardiovascular, and lipid parameters between the end of treatment and the post-cessation period. Random-effects models were used to calculate pooled mean differences. The risk of bias and certainty of evidence were evaluated using the Cochrane ROB 2.0 and GRADE frameworks. The study was registered with PROSPERO under CRD42025646185. Findings Eighteen RCTs (3771 participants) were included. Among individuals with obesity, discontinuation of GLP-1RA resulted in significant metabolic rebound, characterized by a body weight gain of 5.63 kg (95% CI: 3.52–7.73, I2 = 99.57%, moderate) and an increase in HbA1c of 0.25% (95% CI: 0.18–0.32, I2 = 98.45%, moderate). Waist circumference, BMI (Body Mass Index), SBP (Systolic Blood Pressure), and FPG (fasting plasma glucose) also showed significant…
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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 3,771 participants or records.
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