the daily shot before the weekly one
1994–2009 (project launched 1994–95; EU approval 2009, US approval 2010)
The chemist who engineered liraglutide — the molecule that became the blueprint for Ozempic — was originally hired by Novo Nordisk to work on laundry-detergent enzymes, with nothing to do with diabetes at all.
Every GLP-1 drug seems to arrive with the same colorful origin story: a venomous lizard, a lucky accident out in the desert. That story is completely true — but it belongs to a different medicine. The Gila monster tale is the origin of exenatide (Byetta), isolated from the reptile's saliva by endocrinologist John Eng in the early 1990s. Liraglutide's beginning is quieter and, honestly, more impressive: not a discovery in the wild, but a piece of deliberate protein engineering built to solve a plumbing problem.
The engineer at the center of it was Lotte Bjerre Knudsen, who joined Novo Nordisk in 1989 to work on industrial detergent enzymes before a supervisor pulled her onto a small diabetes team as its youngest member. Scientists had characterized GLP-1 in the early 1980s as a gut hormone that, after a meal, tells the pancreas to release insulin in a glucose-dependent way. The catch: an enzyme called DPP-4 shreds GLP-1 within about 1.5 minutes, and the kidneys flush what's left — a hormone with enormous promise and a half-life far too short to ever bottle. Returning from maternity leave in 1994, Knudsen found she was, as she later put it, 'the only one left that knew anything about' the project, and was told to figure out what to do with it.
Her fix was elegant. Clinical data showed GLP-1 needed to be present nearly around the clock to control blood sugar, so Knudsen turned to fatty-acid acylation — bolting a long fatty-acid tail onto GLP-1 so it would cling reversibly to serum albumin, the most abundant protein in blood plasma. Because the kidneys don't filter out albumin, a drug that hitches a ride on it recirculates for hours instead of being flushed in minutes, peeling off slowly to keep working; Novo had already proven the same trick in the insulin drug detemir. The team eventually settled on a 16-carbon palmitic acid attached via a glutamate spacer, plus a single lysine-to-arginine swap to control where the tail attached — though the early versions were so greasy they gummed up the purification columns.
The bigger leap was a hunch about hunger. Knudsen has recounted that rats engineered to chronically overproduce glucagon, GLP-1 and related gut hormones lost their appetites so completely that some starved themselves to death, and when British endocrinologist Stephen Bloom published 1996 work tying GLP-1 to appetite signals in the brain, she asked 'why on earth should we not actually do both things at the same time?' — one molecule for both diabetes and obesity, an idea almost no one else took seriously. The candidate that emerged, internally coded NN2211, became liraglutide: a once-daily injection with a roughly 13-hour half-life, sold as Victoza for type 2 diabetes (EU 2009, US FDA January 2010) and, at a higher 3.0 mg dose, as Saxenda for weight management (2014). It became the direct proof of concept — and the engineering scaffold — for semaglutide, the Ozempic and Wegovy molecule, which swapped in a longer chain to stretch dosing from once-daily to once-weekly.
The starving-rat story is real — it traces to genuine peer-reviewed studies from Novo's own affiliated Hagedorn Research Institute lab — but "starved themselves to death" is Knudsen's own retelling; the papers actually document severe anorexia and near-total loss of food and water intake, not confirmed deaths. She has also given two slightly different versions of exactly which gut hormones those rats overproduced, so that detail is less settled than it sounds.
Liraglutide is now the family's older sibling: still FDA-approved and prescribed, but largely eclipsed commercially by once-weekly semaglutide and tirzepatide, which match or beat its results with a seventh of the injections. Novo Nordisk has reportedly steered manufacturing capacity toward Wegovy and Ozempic, contributing to on-and-off Saxenda shortages in the UK, Canada and Australia through 2024–2025. The headline shift came in August 2025, when the FDA approved the first generic liraglutide injection for weight management (from Teva) — the first generic GLP-1 weight-loss drug in the US, priced roughly 30% below branded Saxenda, a meaningful access point while semaglutide and tirzepatide stay patent-protected into the 2030s. Liraglutide also remains a standard reference comparator in head-to-head GLP-1 trials and is still used in some pediatric and Prader-Willi syndrome settings.
