Wonder Drug? The GLP-1 Story · Episode 1 of 6 · 21 min
The Accidental Blockbuster
The GLP-1 drugs did not begin as weight-loss miracles. They grew from decades of basic research into a faint gut hormone, a chance discovery in Gila monster venom, and protein engineering that made the molecule last. The natural hormone is fragile and cleared from the blood in about two minutes, and the drugs work because they are not nature.
Who's who
- Joel HabenerMassachusetts General Hospital endocrinologist who found glucagon-like sequences inside proglucagon
- Daniel Drucker+2 more episodesJoined Habener's lab in 1984; leading developer and chronicler of the field
- Svetlana MojsovRockefeller peptide chemist who identified and synthesized active GLP-1(7-37)
- Jens Juul HolstCopenhagen physiologist who showed gut GLP-1 secretion and DPP-4 inactivation
- John EngBronx VA physician-researcher who discovered exendin-4 in Gila monster venom
- Lotte Bjerre KnudsenNovo Nordisk scientist whose fatty-acid engineering produced liraglutide and semaglutide
Where it happens
- Massachusetts General Hospital, Boston+2 more episodesWhere Habener isolated proglucagon cDNA using anglerfish islet cells
- Rockefeller University, New YorkWhere Mojsov synthesized and tested GLP-1(7-37)
- University of Copenhagen, DenmarkHolst's lab studied gut secretion and DPP-4 breakdown of GLP-1
- Bronx VA hospital, New YorkWhere John Eng found exendin-4 in the 1990s
Timeline
- Early 1980sHabener isolates cDNA encoding proglucagon and finds glucagon-like sequences within it
- 1987Mojsov, Drucker and Habener show synthesized GLP-1(7-37) stimulates insulin release in rat islets
- Early 1990sJohn Eng discovers exendin-4 in Gila monster venom
- 2005Exenatide (Byetta), synthetic exendin-4, is FDA-approved as the first GLP-1 receptor agonist
- 2021Drucker's review argues gut GLP-1 is not essential for controlling food intake or body weight
- 2024Habener, Mojsov and Knudsen share the Lasker~DeBakey Clinical Medical Research Award
Still debated
Credit for the discovery has been uneven, with Mojsov's role under-recognized for decades. Scientists also still argue how much natural gut GLP-1 matters for body weight and exactly how the drugs cause weight loss.