GLP-1 receptor agonist

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of peptide drugs that mimic the endogenous incretin hormone glucagon-like peptide-1. Endogenous GLP-1 is secreted by intestinal L-cells in response to food intake and acts on pancreatic beta cells to enhance glucose-dependent insulin secretion. It also suppresses glucagon release, slows gastric emptying, and reduces appetite via central receptors in the hypothalamus and area postrema.

Therapeutic use

GLP-1 RAs are first-line therapy for type-2 diabetes and have become first-line pharmacotherapy for obesity. They produce clinically meaningful weight loss (typically 10–20% of body weight on the highest-dose agents) and improvements in HbA1c, cardiovascular risk markers, and several non-diabetic conditions.

Pharmacology

Native GLP-1 has a half-life of approximately two minutes due to rapid cleavage by the enzyme dipeptidyl peptidase-4. Marketed GLP-1 RAs are engineered for resistance to DPP-4: exenatide is a synthetic exendin analogue, liraglutide adds a fatty-acid chain that promotes albumin binding, and semaglutide further modifies the sequence to extend its half-life to roughly one week.

Newer multi-agonists combine GLP-1 activity with agonism at the glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptors. Tirzepatide is a dual GLP-1/GIP agonist; retatrutide is a triple GLP-1/GIP/glucagon agonist in late-stage trials.

”Natty” classification

GLP-1 RAs are not on the WADA prohibited list and are generally considered compatible with natural-bodybuilding standards when used under prescription for a recognised medical indication. Use for purely aesthetic weight management is contested by some federations.

Catalogued GLP-1 agonists on Retapedia