Weight Regain After Discontinuation of High-Dose GLP-1 Receptor Agonists in Adults with Obesity Without Type 2 Diabetes: A Meta-Analysis of Long-Term Follow-Up Studies

Abstract

GLP-1 receptor agonists (GLP-1 RAs) are highly effective for obesity treatment, yet increasing evidence suggests substantial weight regain following treatment discontinuation. Understanding the magnitude and determinants of this regain is critical for long-term obesity management. We conducted a PRISMA-compliant systematic review and meta-analysis of studies published between 2011 and 2025 examining adults with obesity, but without type 2 diabetes, treated with high-dose GLP-1 RAs such as semaglutide 2.4 mg or liraglutide 3.0 mg. Eligible studies reported at least 12 months of follow-up after discontinuation. Random-effects models estimated pooled weight regain, and subgroup analyses compared abrupt vs tapered withdrawal strategies. Eleven studies (n = 12,539 participants) met the inclusion criteria. During active treatment, participants lost 8–17 per cent of baseline body weight. After discontinuation, pooled weight regain at 12 months was 6.52 kg (95 per cent CI, 5.44–7.60), representing 50–65 per cent of lost weight. Statistical heterogeneity was high (I² = 99.7 per cent), but directionality was consistent across all trials. Subgroup analysis showed greater regain after abrupt cessation (7.18 kg) compared with tapering or structured lifestyle maintenance (5.38 kg), p = 0.0378. Conclusion: Discontinuation of high-dose GLP-1 RAs leads to substantial and predictable weight regain. These findings support the need for long-term therapy or structured discontinuation programs to preserve treatment benefits.