Amylin and Amylin Analogs – Future Therapeutic Strategies for the Treatment of Type 2 Diabetes and Obesity

mylin is a peptide hormone co-synthesized with insulin in pancreatic beta cells at a ratio of 1:100. Notably, amylin has a pronounced tendency to form toxic amyloid fibrils, a characteristic relevant to its pathological role. Purpose: This study aims to review both approved amylin analogs (AAs) and those currently in preclinical and clinical development, with a focus on their molecular structure, pharmacokinetics, receptor activity, and metabolic outcomes. Methods: A comprehensive literature review was conducted using PubMed and clinical trial databases. The analysis focused on structure-function relationships of AAs, biotechnological modifications influencing pharmacokinetics, receptor pharmacology (AMY 1-3), and their effects on glycemic control and appetite. Results: Pramlintide, approved by the FDA in 2005, delays gastric emptying, suppresses postprandial glucagon secretion, improves HbA1c, and induces modest weight loss. Dual amylin-calcitonin receptor agonists (DACRAs) represent next-generation drugs. Davalintide, in phase II trials, has demonstrated reductions in food intake, body weight, and HbA1c. It was ultimately discontinued due to insufficient efficacy and an unfavorable tolerability profile. KBP-089 and KBP-088 have shown favorable metabolic and hepatic effects in preclinical studies. Cagrilintide, a long-acting amylin analog combined with semaglutide (CagriSema), is currently in phase III clinical trials, showing significantly greater weight loss and improved glycemic control compared to monotherapy. Novel investigational agents, including NN1213, eloralintide, petrelintide, MET-233i, and amycretin, have demonstrated substantial weight loss, signaling a new era in amylin-based obesity pharmacotherapy. Conclusion: Amylin analogs present a compelling dual-targeted approach for managing T2D and obesity by improving both glycemic control and weight outcomes. Ongoing clinical trials will further define their long-term therapeutic role.