Drug Discovery Today · Oct 27, 2026

Incretin and nutrient-sensing GPCR therapeutics in type 2 diabetes: what target-modality-formulation matching explains

By Seo Y, Woo J

Receptor-directed therapeutics now dominate type 2 diabetes, yet their clinical value depends on more than target biology. This review proposes a pharmaceutics-centered framework spanning the receptors for glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and glucagon, amylin co-agonism and selected nutrient-sensing receptors, it then tests against a defined cohort of 49 programs that reached Phase II in type 2 diabetes. Among arrests with a disclosed scientific cause, modality predominates; two-thirds of arrests were unexplained or attributed to portfolio decisions. Deliverability discriminates among comparable mechanisms, cannot raise a low receptor ceiling and is poorly served by the public record.

doi.org/10.1016/j.drudis.2026.104843PubMed 42946155Interventions