Incretin

Incretin

Incretins are gut hormones that boost the insulin response to glucose taken by mouth. The name comes from “intestinal secretion of insulin.” It was coined to describe the finding that oral glucose produces a bigger insulin response than the same amount given into a vein, known as the incretin effect. The two main incretins in humans are GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide).

Together, GLP-1 and GIP account for about 50-70% of the insulin released after a meal in healthy people. The incretin effect is clearly weaker in people with type 2 diabetes, which helps explain poor blood sugar control after meals. Recognizing that incretin pathways are deficient in diabetes led to incretin-based drugs, now one of the most important drug classes in metabolic medicine.

Incretin-based drugs come in two types. DPP-4 inhibitors stop the body’s own incretins from being broken down. Incretin receptor agonists activate incretin receptors directly at drug-level concentrations. The second group, which includes semaglutide, tirzepatide and retatrutide, has produced some of the biggest advances in diabetes and obesity treatment in recent decades. Retatrutide takes the incretin idea further by adding glucagon receptor activity to GIP and GLP-1 receptor activity.