GLP-1 (Glucagon-Like Peptide-1)

GLP-1 (Glucagon-Like Peptide-1) is a 30-amino acid incretin hormone secreted by intestinal L cells in response to nutrient ingestion. Discovered in the 1980s as an alternative cleavage product of preproglucagon, it has since the 2010s become the most exploited pharmacological target in modern metabolic medicine history, with a succession of analogues having transformed the treatment of type 2 diabetes and then obesity.

Physiologically, GLP-1 exerts four major actions mediated by its GLP-1R receptor, a member of the class B G-protein coupled receptor (GPCR) family. First, it amplifies insulin secretion by pancreatic β cells in a glucose-dependent manner, which explains the absence of severe hypoglycemia with GLP-1 agonists: the effect subsides when glycemia decreases. Second, it suppresses glucagon secretion by pancreatic α cells. Third, it slows gastric emptying, prolonging postprandial satiety. Fourth, it acts at the hypothalamic level to reduce appetite and food intake.

Native GLP-1 is extremely short-lived in vivo: it is rapidly degraded by the DPP-4 enzyme (dipeptidyl peptidase-4) which cleaves the first two amino acids (His-Ala), producing an inactive metabolite. Its plasma half-life of only 1 to 2 minutes long prevented its direct pharmacological use. Researchers circumvented this limitation through two strategies: pharmacological inhibition of DPP-4 (sitagliptin, vildagliptin) to prolong endogenous GLP-1, or development of DPP-4-resistant analogues.

Modern GLP-1 analogues integrate structural modifications to extend half-life from minutes to days. Liraglutide adds a palmitic fatty acid enabling reversible binding to serum albumin (half-life ≈13h, daily administration). Semaglutide introduces a substitution at position 8 (Aib replacing alanine) rendering the peptide DPP-4-resistant, combined with a modified C18 fatty acid for prolonged albumin binding (half-life ≈1 week, weekly administration). Tirzepatide innovates by co-agonizing both GLP-1R and GIP-R (GIP receptor), offering superior metabolic effects. Retatrutide pushes the logic as a triple-agonist GLP-1/GIP/glucagon.

On lab-peptides-france.com, the GLP-1 research range comprises semaglutide, tirzepatide and retatrutide in various doses, intended exclusively for laboratory uses (RUO, Research Use Only). These peptides enable researchers to explore the molecular mechanisms of the incretin axis, pharmacological differences between selective agonists and multi-agonists, and biased signaling pathways of the GLP-1R receptor in controlled in vitro and animal in vivo conditions.