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The Incretin Story

How one peptide fragment became the biggest drug class of the decade

A discovery that took decades to credit

In the 1980s, Svetlana Mojsov — working in the peptide-synthesis tradition Merrifield founded — synthesized glucagon-family peptides and pinned down the truly bioactive incretin sequence, GLP-1(7-37), the 31-amino-acid fragment that actually stimulates insulin.1 That identification is the seed of the entire GLP-1 drug class; she received a 2024 Lasker~DeBakey Award.2

What the 'incretin effect' is

Incretins are gut hormones released when you eat. They produce glucose-dependent insulin release (insulin only when sugar is high — hence low hypoglycemia risk), suppress glucagon, slow gastric emptying, and signal satiety to the brain. Turning that biology into a durable drug required half-life engineering.

The lineage

GenerationTargetsExamples
Single agonistGLP-1Semaglutide
Dual ("twincretin")GLP-1 + GIPTirzepatide
TripleGLP-1 + GIP + glucagonRetatrutide (investigational)
Oral small-moleculeGLP-1Orforglipron (investigational)
The pattern: each generation adds a complementary pathway. It's the clearest real-world example of rational, receptor-by-receptor drug design — and why the science in the GPCR chapter pays off.

Further reading — primary sources

  1. The discovery of GLP-1 and its therapeutic legacy. PNAS
  2. GLP-1-based therapy for obesity — Lasker citation. laskerfoundation.org
  3. GLP-1 mechanisms & development — Harvard HMS CME. learn.hms.harvard.edu

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For educational and research purposes only. This content is not medical advice. Compounds referenced are research use only unless noted as approved drugs, and nothing here is an instruction to use, prepare, or administer anything. Free Peptide University does not sell compounds.