Weight Regain After Bariatric Surgery: Anatomical, Metabolic, and Behavioral Mechanisms and the Role of GLP-1/GIP Therapy

Abstract

Weight gain after bariatric surgery is a clinically documented phenomenon affecting up to 49% of patients within five years, threatening the long-term efficacy of an intervention that currently ranks as the most effective treatment for severe obesity. This narrative review examines the intersecting anatomical, metabolic, and behavioral mechanisms underlying post-bariatric weight recidivism and evaluates the emerging role of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists in its management. The methodology integrated a systematic search of PubMed, Scopus, and Web of Science databases (2020-2026), selecting 25 peer-reviewed sources including randomized controlled trials, meta-analyses, and prospective cohort studies. Anatomical changes such as gastric pouch or sleeve dilation contribute structurally to regain, while metabolic adaptation, ghrelin rebound, and leptin resistance create a persistent physiological drive toward weight restoration. Behavioral factors, including driven overeating, emotional eating, and dietary non-adherence, compound these biological pressures. GLP-1 receptor agonists (liraglutide, semaglutide) and the dual GLP-1/GIP agonist tirzepatide have demonstrated clinically meaningful weight reduction of 7-13.6% of total body weight in post-bariatric patients with weight regain. Based on the evidence synthesis, this review proposes an original Three-Domain Assessment Model and an integrated, stepwise clinical protocol for post-bariatric weight management. The findings are relevant to bariatric surgeons, obesity medicine physicians, endocrinologists, and primary care practitioners managing patients with long-term post- surgical weight challenges.