Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual/triple co-agonists have revolutionized obesity treatment, producing mean weight losses of 10-30% that were rarely achievable with lifestyle modification or earlier medications. Yet, once GLP-1 therapy is discontinued, most patients experience rapid weight regain, often accompanied by reversal of cardiometabolic improvements. Real-world data show that up to 65% of users discontinue GLP-1 RAs within a year of initiation, and randomized controlled trials demonstrate that two-thirds of lost weight is typically regained within a year of discontinuation. Weight regain following GLP-1 RA discontinuation reflects a powerful interplay of physiological, behavioral, and environmental factors that promote relapse once pharmacological appetite suppression is removed. Sustaining weight loss after GLP-1 RA discontinuation will ultimately depend on integrated, patient-centered frameworks combining ongoing lifestyle, behavioral, and system-level supports.
Keywords: Glucagon-like peptide-1 receptor agonist; Maintenance; Pharmacotherapy discontinuation; Weight cycling; Weight rebound.
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