Appetite Dysregulation as a Driver of Weight Regain After GLP-1 Receptor Agonist-Induced Weight Loss: A Systematic Review

Background: GLP-1 receptor agonists and related incretin-based therapies are effective pharmacological treatments for weight loss in adults with obesity and type 2 diabetes. However, weight regain after treatment discontinuation or attenuation remains a major clinical challenge. Appetite dysregulation may be one mechanism contributing to this regain. Objective: This systematic review aimed to evaluate whether appetite-related changes contribute to weight regain following GLP-1-based weight loss, with particular attention to the distinction between direct post-treatment evidence and indirect evidence from active-treatment studies. Methods: A systematic literature search was conducted in PubMed, Scopus, Embase, and the Cochrane Library for studies published between 2016 and 2026, following PRISMA 2020 guidelines. Eligible studies included adults with obesity, overweight, and/or type 2 diabetes receiving GLP-1 receptor agonists or related incretin-based therapies and reporting appetite-related outcomes, weight outcomes, weight maintenance, or weight regain. Randomized controlled trials, clinical trials, crossover studies, and observational studies were included. Findings were synthesized qualitatively. Results: Eighteen studies published between 2017 and 2026 met the inclusion criteria. Most studies reported that GLP-1-based therapy reduced appetite, hunger, food cravings, energy intake, or dietary intake, while increasing satiety and promoting weight loss during active treatment. Direct appetite measures were commonly reported using visual analogue scales, appetite questionnaires, food craving measures, and energy intake assessments. However, only a small number of studies directly evaluated appetite changes during treatment withdrawal, weight maintenance, or post-treatment weight regain. Therefore, the available evidence supports a plausible mechanistic link between loss of appetite regulation and weight regain, but the evidence remains largely indirect. Conclusion: GLP-1-based therapies consistently improve appetite regulation and promote weight loss during active treatment. However, direct evidence linking post-treatment appetite dysregulation to subsequent weight regain remains limited. Appetite dysregulation should therefore be interpreted as a plausible and clinically relevant contributor, rather than a definitively established causal driver.