GLP-1

Glucagon-Like Peptide-1

GLP-1 (glucagon-like peptide-1) is one of the body’s two main incretin hormones; the other is GIP. L-cells in the lining of the lower small intestine and colon release it when you eat. Once in the bloodstream, GLP-1 acts on GLP-1 receptors throughout the body, including in pancreatic beta cells, the brain, the gut and the cardiovascular system.

GLP-1 does several things. In the pancreas, GLP-1 boosts glucose-dependent insulin release and lowers glucagon release from alpha cells, both of which lower blood glucose. In the brain, GLP-1 receptors in the hypothalamus and brainstem curb appetite and signal fullness, which is the main reason GLP-1 receptor agonists cause weight loss. GLP-1 also slows gastric emptying, which blunts blood sugar rises after meals and makes you feel full for longer.

Natural GLP-1 lasts only about two minutes in the blood, because the enzyme dipeptidyl peptidase-4 (DPP-4) breaks it down quickly. That led to the development of GLP-1 receptor agonists that resist DPP-4, such as semaglutide and liraglutide, now widely used for type 2 diabetes and obesity. Retatrutide includes GLP-1 receptor activity as one part of its triple agonist action, alongside GIP and glucagon receptor activity.

Over the past decade, the GLP-1 receptor has become the most clinically proven target in metabolic medicine. In retatrutide, it mainly drives lower appetite, better blood sugar control and the improvements in cardiovascular risk factors seen in clinical trials. Retatrutide has not yet shown a reduction in cardiovascular events; its outcomes trial, TRIUMPH-Outcomes, is running.