GLP1

GLP-1, or glucagon-like peptide-1, is an incretin hormone produced by enteroendocrine L-cells of the small intestine and colon, and by certain neurons in the brainstem. It is derived from the proglucagon peptide and exists mainly as the active form GLP-1 (7–36) amide in circulation, although dipeptidyl peptidase-4 rapidly degrades it to shorter, less active fragments. The native circulating half-life is short, on the order of minutes.

GLP-1 exerts its effects through the GLP-1 receptor, a Gs-protein–coupled receptor expressed on pancreatic beta cells, alpha cells, the central nervous system, and various peripheral tissues. In response to meals, GLP-1 enhances glucose-dependent insulin secretion from beta cells, suppresses glucagon release from alpha cells, slows gastric emptying, and promotes satiety. These actions help coordinate postprandial glucose control and contribute to energy balance and appetite regulation.

Physiologically, GLP-1 is a key component of the incretin effect, whereby oral nutrients provoke a greater insulin response than an equivalent intravenous glucose load. The rapid breakdown by DPP-4 limits native GLP-1 activity, which has driven the development of pharmacologic agents that modulate this pathway.

Clinically, GLP-1 receptor agonists (for example, exenatide, liraglutide, dulaglutide, and semaglutide) are used to treat type 2 diabetes and, in some formulations, obesity. They provide meaningful reductions in HbA1c and often promote weight loss. DPP-4 inhibitors (gliptins) prolong endogenous GLP-1 levels to achieve similar, often more modest, glucose-lowering effects. Common adverse effects are gastrointestinal; there are rare concerns about pancreatitis and cholelithiasis. Research continues into cardiovascular and potential neuroprotective benefits.