Advances in Pharmacology · Oct 21, 2026

Future directions in obesity pharmacotherapy: Novel targets and pipeline therapies

By Mauer Y, Isaacs D

Obesity medications counteract the body's adaptive mechanisms to weight loss, which result in increased hunger and food cravings, reduced satiety, and decreased energy expenditure. Second generation obesity pharmacotherapy includes nutrient-stimulated hormone (NuSH)-based therapies. Specifically, GLP-1 RA have demonstrated significant and persistent weight loss and include the FDA approved therapies semaglutide and liraglutide. Tirzepatide is a dual GLP-1 and GIP RA that has demonstrated even more weight loss and metabolic benefits. Future directions in obesity pharmacotherapy include more co-agonist therapies targeting glucagon receptors as well as triple agonists targeting GLP, GIP and glucagon receptors like retatrutide. Amylin-based agents complement GLP-1 RA as demonstrated by cagrilinitide-semaglutide. Additionally, oral agents with increased bioavailability are on the horizon like orforglipron along with agents that may help preserve muscle mass like bimagrumab. NuSH-based therapies with monthly dosing like MariTide are also being researched. This chapter explores the future directions in obesity pharmacotherapy including the novel targets and pipeline therapies in phase 2 and phase 3 development.

doi.org/10.1016/bs.apha.2026.06.003PubMed 42977350Interventions