GLP-1 (Glucagon-Like Peptide-1)

Deep dive

GLP-1 (Glucagon-Like Peptide-1): complete reference

Glucagon-like peptide-1 (GLP-1) is a 30-amino-acid incretin hormone discovered in 1985 and secreted by intestinal L-cells primarily in the distal small intestine and colon in response to nutrient intake. Within minutes of eating, GLP-1 levels rise sharply, peaking around 30-60 minutes post-meal before being rapidly degraded by dipeptidyl peptidase-4 (DPP-4) — native GLP-1 has a circulating half-life of only 1-2 minutes. Its physiological effects are multi-organ: stimulating glucose-dependent insulin secretion from pancreatic beta cells, suppressing glucagon release from alpha cells, slowing gastric emptying to prolong nutrient absorption, and acting on hypothalamic and brainstem appetite centers to promote satiety. The discovery that incretin signaling is impaired in type 2 diabetes led to the development of pharmaceutical GLP-1 receptor agonists — modified peptides resistant to DPP-4 degradation that can sustain receptor activation for hours (daily injections) or days (weekly injections). This pharmacology underlies semaglutide, tirzepatide, liraglutide, dulaglutide, and exenatide, which now collectively constitute one of the largest drug categories in the US by sales.

In practice

When you finish a meal, your gut releases GLP-1 that tells your pancreas to produce insulin, slows your stomach so food stays longer, and signals your brain that you're full. GLP-1 medications mimic this signal continuously.

Clinical context

Clinicians use GLP-1 receptor agonists as first- or second-line therapy for type 2 diabetes (after metformin) and as primary pharmacotherapy for chronic weight management in patients with obesity.