Melina I Manolas, Robert S Brown
Metabolic dysfunction, manifesting as obesity, type 2 diabetes mellitus (T2DM), and related cardiometabolic comorbidities, has emerged as a major driver of morbidity among patients with advanced liver disease and liver transplant (LT) recipients. These conditions influence disease progression, transplant candidacy, perioperative risk, and long-term graft and patient outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become cornerstone treatments for obesity and T2DM, with benefits extending beyond glycemic control to include sustained weight loss, improved insulin sensitivity, and reduction in cardiovascular risk. These pleiotropic metabolic effects are highly relevant across the LT continuum, where metabolic disease frequently complicates management both before and after transplant. Historically, adoption of GLP-1RA-based therapies in patients with cirrhosis and in LT recipients has been limited by concerns regarding gastrointestinal tolerability, nutritional status, frailty, and potential interactions with immunosuppressive medications. Emerging observational studies suggest that GLP-1RAs may safely improve glycemic control and support weight management before and after LT, although prospective transplant-specific trials remain needed. This article summarizes the mechanistic rationale, current clinical evidence, and practical considerations for GLP-1RA use in patients with advanced liver disease and LT recipients and highlights key knowledge gaps as well as future research priorities in transplant hepatology.