Glucagon
Overview
A 29-amino acid peptide hormone produced by alpha cells of the pancreatic islets of Langerhans. Glucagon acts primarily on hepatocytes via the glucagon receptor (GCGR), a G-protein-coupled receptor that activates adenylyl cyclase, increasing cAMP and triggering glycogenolysis and gluconeogenesis to raise blood glucose. It also relaxes smooth muscle of the GI tract and has positive inotropic and chronotropic cardiac effects.
Key Research Findings
FDA-approved for treatment of severe hypoglycemia and as a diagnostic aid for radiologic examination of the GI tract. Newer formulations include nasal glucagon (Baqsimi, 2019) and ready-to-use liquid glucagon (Gvoke, 2019), improving ease of emergency administration. Glucagon receptor antagonists are under investigation for type 2 diabetes.
Subcutaneous injection, Intramuscular injection, Intranasal
FDA Approved
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Semaglutide (Ozempic/Wegovy)
FDA ApprovedA glucagon-like peptide-1 receptor agonist (GLP-1 RA) with 94% amino acid homology to native GLP-1. Semaglutide enhances glucose-dependent insulin secretion, suppresses glucagon, delays gastric emptying, and acts on hypothalamic GLP-1 receptors to reduce appetite. Its fatty acid side chain enables albumin binding, extending its half-life to approximately 7 days.
Tirzepatide (Mounjaro/Zepbound)
FDA ApprovedA first-in-class dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. Tirzepatide activates both incretin pathways simultaneously, producing superior glycemic control and weight loss compared to selective GLP-1 RAs. The dual mechanism enhances insulin sensitivity and lipid metabolism beyond what either pathway achieves alone.
Retatrutide
In Clinical TrialsAn investigational triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. The glucagon receptor component adds thermogenic energy expenditure and hepatic lipid mobilization to the incretin-mediated appetite suppression and insulin sensitization. This triple mechanism addresses obesity through complementary metabolic pathways.
AOD-9604
InvestigationalA modified 16-amino acid fragment (amino acids 176-191) of the C-terminus of human growth hormone with an added tyrosine at the N-terminus. AOD-9604 retains the lipolytic activity of hGH without its growth-promoting or diabetogenic effects. It stimulates lipolysis and inhibits lipogenesis through a mechanism distinct from the GH receptor, acting on beta-3 adrenergic receptors in adipose tissue.