Glucagon-like peptide-1 receptor agonists as a metabolic optimization strategy in surgical prehabilitation: a translational perspective.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide and tirzepatide, are increasingly prescribed for obesity and type 2 diabetes and have demonstrated substantial and rapid weight loss in large randomized trials. At the same time, prehabilitation before major abdominal surgery has become an established perioperative strategy to improve postoperative outcomes. This review explores the potential role of GLP-1RAs as a pharmacological adjunct in multimodal surgical prehabilitation. We discuss the biological rationale for metabolic optimization, the relevance of sarcopenic obesity, potential implications for oncological surgery and neoadjuvant therapy, and emerging data from bariatric and metabolic surgery. We also highlight important perioperative safety considerations, particularly delayed gastric emptying and aspiration risk, and current anesthetic guidance. Although integration of GLP-1RAs into prehabilitation pathways is biologically plausible and clinically attractive, there is currently no direct evidence supporting their use in this setting. We propose that GLP-1RAs represent a promising and testable strategy for metabolic optimization in surgical patients. Prospective studies are required to evaluate feasibility, safety, and impact on clinically meaningful outcomes. This framework is hypothesis-generating and aims to inform future translational research at the interface of metabolic medicine and perioperative care.