Hormones · 18 min read
GLP-1 Receptor Agonists: From Peptide to Blockbuster Drug
Tracing the journey of GLP-1 from its discovery as an incretin hormone to the development of semaglutide and tirzepatide in metabolic medicine.
The Incretin Effect and GLP-1 Discovery
GLP-1 research began with the incretin effect: oral glucose produces a greater insulin response than equivalent intravenous glucose. GLP-1 is a gut-derived peptide hormone that signals through GLP-1 receptors in multiple tissues.
Physiological Actions of GLP-1
GLP-1 stimulates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and influences appetite and satiety. Preclinical work also explores beta-cell and cardiovascular effects.
Engineering Longer-Acting Analogs
Native GLP-1 has a short half-life, motivating development of DPP-4-resistant analogs. Exenatide, liraglutide, and semaglutide illustrate successive approaches to extending peptide activity.
Tirzepatide and Multi-Receptor Agonism
Tirzepatide activates both GIP and GLP-1 receptors. Research into multi-receptor agonism has expanded to triple agonists that also target glucagon receptors.
Impact and Future Directions
GLP-1 receptor agonists have transformed metabolic medicine. Ongoing research is examining additional applications and refining peptide delivery and receptor selectivity.