Effects of Glucagon-Like Peptide-1 Receptor Agonists After Treatment Withdrawal: A Systematic Review and Meta-Analysis.

Abstract

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. 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. 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/m², 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/m², 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/m², 95% CI: -1.47 to -0.17). 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.