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The full episode, in writing.
The active molecule behind Ozempic, Wegovy, Mounjaro, and Zepbound did not start in a lab. It started in the venom of a Gila monster — a slow, fat-tailed lizard that lives in the Sonoran Desert and eats only once or twice a year. In the 1980s, a postdoc named Jean-Pierre Raufman at the National Institutes of Health was working for John Pisano, a biochemist who collected animal venoms looking for novel substances that affected human physiology. Raufman focused on the Gila monster because its eating schedule fascinated him. He found that its venom contained molecules that inflamed the pancreas of test animals.
In 1992, an endocrinologist named John Eng at the Bronx VA Medical Center used radioimmunoassay to isolate one of those molecules. He called it exendin-4. It looked like a long-acting version of a human gut hormone called GLP-1, glucagon-like peptide-1, which the small intestine releases after a meal. Native human GLP-1 has a half-life of about two minutes — an enzyme called DPP-4 chops it apart almost as fast as the body makes it. That short half-life had killed every previous attempt to turn GLP-1 into a drug. Exendin-4 lasted for hours. Eng filed a patent in 1993, then spent three years cold-calling pharmaceutical companies. Every one passed. In 1996, a small biotech called Amylin Pharmaceuticals licensed it.
The FDA approved exendin-4 as Byetta in April 2005, manufactured jointly with Eli Lilly, for type 2 diabetes. It worked by activating the GLP-1 receptor — sites on pancreatic beta cells, sites in the hypothalamus, sites scattered through the gut and the brain. Activation slows gastric emptying, blocks glucagon release, stimulates insulin, and dampens appetite signals. Byetta had to be injected twice a day, and a third of patients developed antibodies against it that reduced its effect. But it proved the receptor was a viable drug target. Other companies poured in.
Novo Nordisk, a Danish insulin maker, developed liraglutide. The FDA approved it in 2010 for diabetes as Victoza, then in 2014 for weight management as Saxenda. Eli Lilly's dulaglutide, branded Trulicity, came in 2014 with weekly dosing. Then Novo Nordisk released semaglutide — Ozempic for diabetes in 2017, an oral version called Rybelsus in 2019, and Wegovy specifically for obesity in 2021. Semaglutide produced average weight loss of around 15% in trial participants. Eli Lilly's tirzepatide, approved as Mounjaro for diabetes in 2022 and Zepbound for obesity in late 2023, hit a different target combination — both the GLP-1 receptor and the GIP receptor — and pushed average weight loss above 20%. By 2024, more than a third of trial participants on tirzepatide had lost a fifth of their body weight.
Demand outran supply. The FDA declared shortages of semaglutide, tirzepatide, dulaglutide, liraglutide, and exenatide in 2022. Compounding pharmacies, legally allowed to make custom versions of drugs in declared shortage, started producing copycat semaglutide and tirzepatide. By January 2026, Novo Nordisk's CEO Mike Doustdar told Reuters that as many as 1.5 million people in the United States were using compounded versions. Gray-market sellers and online clinics sold unregulated knockoffs to anyone with a credit card. The tirzepatide shortage officially ended in 2024, but the compounded supply chain did not.
The economic effect was enormous. Novo Nordisk became the most valuable company in Europe in 2024, with a market capitalization of $570 billion — larger than the entire gross domestic product of Denmark. Its $2.3 billion income tax bill made it the country's largest single taxpayer, and its growth accounted for nearly all of Denmark's economic expansion that year. By October 2024, Eli Lilly had become the world's most valuable drug company, on the back of tirzepatide.
The drugs are not benign. The FDA requires a boxed warning for thyroid C-cell tumors based on rodent data, and the drugs are contraindicated in anyone with a personal or family history of medullary thyroid cancer. Common side effects are gastrointestinal — nausea reported in up to three-quarters of patients on short-acting versions. A 2025 study linked semaglutide to non-arteritic anterior ischemic optic neuropathy, a rare cause of sudden vision loss. Gallstones form during rapid weight loss. Anesthesiologists in 2024 began telling patients to skip a weekly dose before surgery because delayed gastric emptying raised aspiration risk. And weight loss reverses fast: 50 to 70% of lost weight returns within a year of stopping, and most people are back to baseline within 18 months.
Cost is the other ceiling. In the United States, cost was the cited reason for stopping the drugs in 48.6% of patients who quit. A 2025 estimate put the price of full Medicare coverage for obesity at $69.5 billion over a decade. The Trump administration declined to finalize a Biden-era proposal to require Medicare and Medicaid coverage in April 2025, then reversed direction in November and announced TrumpRx, lowering the price to $245 a month for Medicaid and CHIP patients and $50 a month for Medicare patients in opted-in states. In December 2025, CMS announced the Medicare GLP-1 Bridge, a demonstration program running from July 1 to December 31, 2026, giving eligible Part D beneficiaries Wegovy and Zepbound at $50 per month. The longer-term BALANCE Model is scheduled for January 2027. In November 2025, Novo Nordisk reported topline results from its evoke and evoke+ trials testing semaglutide against Alzheimer's progression. Both failed.