Amylin Analogs: The Next Major Class of Weight Loss Therapy: A Review of Experimental Data and Early-Phase Clinical Trials.

AIMS: The management of the disease of obesity has been transformed by incretin-based therapies; however, additional and alternative therapeutic strategies are needed to address its biological complexity. This narrative review examines the physiology of amylin and the emerging role of amylin-based therapies in obesity management. MATERIALS AND METHODS: We conducted a narrative review of amylin-based therapies that were approved or remained in human clinical development for obesity as of 30 April 2026. PubMed/MEDLINE, ClinicalTrials.gov, Google Scholar, company press releases, investor reports, and major congress abstracts were searched for relevant preclinical and clinical evidence. RESULTS: Amylin, co-secreted with insulin from pancreatic β-cells, slows gastric emptying, suppresses glucagon secretion, and promotes meal termination through central mechanisms. Pramlintide, the first approved amylin analogue, established proof of concept but was limited by modest efficacy and frequent dosing. More recently, long-acting amylin-based therapies, including cagrilintide, eloralintide, petrelintide, MET-233i, ABBV-295, and AZD6234, as well as combination approaches such as cagrilintide with semaglutide and zenagamtide, have demonstrated clinically meaningful weight loss with generally favorable tolerability profiles. CONCLUSIONS: Amylin-based therapies represent a promising addition to the evolving treatment landscape of obesity. Their emerging efficacy as both standalone and combination therapies supports a multi pathway approach to addressing the biological complexity and heterogeneity of the disease.