Incretin

Incretin

Incretins are gastrointestinal hormones that enhance the insulin response to oral glucose intake. The term derives from “intestinal secretion of insulin” and was coined to describe the observation that oral glucose produces a greater insulin response than an equivalent intravenous glucose load, a phenomenon known as the incretin effect. The two primary incretins identified in humans are GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide).

Together, GLP-1 and GIP are responsible for approximately 50-70% of the insulin secreted after a meal in healthy individuals. This incretin effect is notably diminished in people with type 2 diabetes, contributing to impaired postprandial glucose regulation. The recognition that incretin pathways are deficient in diabetes led to the development of incretin-based therapies, which now represent one of the most important classes of medications in metabolic medicine.

Incretin-based therapeutics fall into two categories: DPP-4 inhibitors (which prevent the degradation of endogenous incretins) and incretin receptor agonists (which directly activate incretin receptors at pharmacological concentrations). The latter category, which includes semaglutide, tirzepatide, and retatrutide, has produced some of the most significant advances in diabetes and obesity treatment in recent decades. Retatrutide extends the incretin concept beyond its traditional boundaries by incorporating glucagon receptor agonism alongside GIP and GLP-1 receptor activity.