Amylin analogs for the treatment of obesity without diabetes: present and future

Obesity is a pandemic, linked with increased morbidity including diabetes mellitus (DM) and certain cancer types. Amylin is a major regulatory hormone for satiation and food intake perception in humans. Amylin analogs (pramlintide and cagrilintide) are emerging as promising anti-obesity agents in non-DM subjects.

Pramlintide, the first amylin analog, initially used for the treatment of both type 1 and type 2 DM, has demonstrated weight-lowering action. Clinical trials confirmed a weight loss exceeding 3% in the study period without major untoward effects, which was maintained beyond the follow-up period. Recently, cagrilintide, a long-lasting synthetic amylin analog has been introduced. Cagrilintide has achieved adequate weight loss, reaching even more than 10% of the total weight in early clinical trials. However, adverse gastrointestinal effects, particularly nausea, were more frequent compared with pramlintide. Clinical trials have also confirmed the effectiveness of cagrilintide in comparison with glucagon-like peptide 1 receptor agonists.

Amylin analogs will certainly enrich the growing therapeutic armamentarium aimed at tackling obesity. The most exciting future research venue could be the development of their combinations with other weight-lowering drugs, especially dual and triple incretin-based co-agonists, thus potentially providing massive weight-loss effects.