BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively promote weight reduction and improve glycemic control, blood pressure, and lipid profiles in individuals with overweight or obesity. This systematic review and meta-analysis evaluates the durability of these therapeutic benefits following treatment discontinuation.
METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP from inception to June 2024, to identify randomized controlled trials that assessed the effects of GLP-1RAs with a follow-up period of at least six months after treatment discontinuation. The outcomes were changes in weight, body mass index (BMI), waist circumference (WC), glycemia, blood pressure, and lipid profiles.
RESULTS: We screened 10,670 studies and ultimately identified 5 eligible studies, encompassing 719 patients. Compared to the control group, GLP-1RAs were associated with significant reductions in weight (mean difference (MD) = -5.70 kg, 95% confidence interval (CI): -9.52 to -1.88), BMI (MD = -2.94 kg/m, 95% CI: -5.60 to -0.28), WC (MD = -3.66 cm, 95% CI: -4.89 to -2.43), glycated hemoglobin A1c (HbA1c) (standardized mean difference (SMD) = -0.73, 95% CI: -1.14 to -0.32), and systolic blood pressure (SBP) (MD = -3.62 mm Hg, 95% CI: -5.51 to -1.73) after cessation of therapy. After discontinuation, there was a pronounced rebound in weight (MD = 4.13 kg, 95% CI: 1.60 to 6.65), BMI (MD = 0.84 kg/m, 95% CI: 0.37 to 1.32), WC (MD = 3.64 cm, 95% CI: 2.27 to 5.01), and HbA1c (SMD = 0.69, 95% CI: 0.50 to 0.89). From study baseline to the end of follow-up, GLP-1RAs treatment resulted in statistically significant decreases in weight (MD = -2.32 kg, 95% CI: -4.21 to -0.43) and BMI (MD = -0.82 kg/m, 95% CI: -1.47 to -0.17). 2 2 2
CONCLUSIONS: This meta-analysis demonstrated that although statistically significant weight reduction persists after GLP-1RAs discontinuation, the clinical significance and durability of this effect are limited. To achieve sustained therapeutic benefits, continued treatment with these agents may be necessary.
