Ozempic exists because of a gut hormone discovered in the 1980s that turned out to do far more than anyone initially expected. The story stretches across three decades, from basic laboratory research on the genetics of glucagon to a billion-dollar weekly injection, and it involves a chain of scientists whose work built on each other in ways none of them fully anticipated.
The Hormone That Started It All
In the early 1980s, Joel Habener’s laboratory at Massachusetts General Hospital was using new DNA technology to study glucagon, a hormone the pancreas releases to raise blood sugar. By sequencing the gene that codes for glucagon, Habener’s team discovered something unexpected: the same gene also contained instructions for two additional, previously unknown hormone fragments. These were eventually named glucagon-like peptide 1 and glucagon-like peptide 2, or GLP-1 and GLP-2.
The next question was whether these fragments actually did anything in the body. Svetlana Mojsov, a chemist working in Habener’s lab, identified the precise forms of GLP-1 that the body produces, detecting both full-length and shortened versions of the peptide in pancreatic tissue. This was painstaking chemical work, and it mattered enormously. The shortened form, GLP-1(7-36)amide, turned out to be the biologically active one.
By 1987, two things happened almost simultaneously. Jens Juul Holst and colleagues in Copenhagen demonstrated that this truncated form of GLP-1 was a powerful trigger for insulin release, identifying it as a new “incretin” hormone, a substance released by the gut that tells the pancreas to produce insulin after a meal. That same year, researchers in London confirmed the effect worked in humans. A natural hormone had been found that could lower blood sugar, and it only worked when blood sugar was already elevated, which meant a low risk of causing dangerous drops in blood sugar.
Why the Natural Hormone Wasn’t Enough
GLP-1 looked like a dream candidate for treating type 2 diabetes, but it had a crippling limitation. The body breaks it down within minutes. An enzyme called DPP-4 chews through GLP-1 so quickly that injecting the natural hormone would require continuous infusion, making it impractical as a medication.
This created a race to engineer a version of GLP-1 that could survive in the bloodstream long enough to be useful. One early approach came from an unexpected source: the saliva of the Gila monster, a venomous lizard native to the American Southwest. A compound called exendin-4, found in the lizard’s venom, mimics GLP-1 but resists breakdown. It became the basis for exenatide (Byetta), the first GLP-1 drug approved in 2005. But exenatide shared only about 53% of its structure with human GLP-1 and required twice-daily injections.
Novo Nordisk, the Danish pharmaceutical company, took a different path. Rather than borrowing from lizard biology, their scientists worked to modify the human GLP-1 molecule itself, keeping it as close to the natural hormone as possible while making it last longer in the body.
Lotte Bjerre Knudsen and the Novo Nordisk Team
In the mid-1990s, Lotte Bjerre Knudsen, a young scientist in Novo Nordisk’s chemical division, joined a small group dedicated to developing GLP-1 into a real drug. By 1995, she was leading it. The team’s first major success was liraglutide, which shares 97% of its structure with human GLP-1. They attached a fatty acid chain to the molecule that allows it to bind to albumin, a protein in the blood, slowing its clearance from the body. This extended liraglutide’s useful life to 11 to 13 hours, enough for a once-daily injection. It was approved in 2010 under the brand name Victoza.
But once daily still wasn’t ideal. Knudsen and a team of Novo Nordisk chemists led by Jesper Lau and Thomas Kruse set out to create a version that could be injected just once a week. The result was semaglutide. It shares 94% of its structure with human GLP-1 but incorporates two key amino acid substitutions. One, at position 8, specifically protects the molecule from being broken down by DPP-4. A longer fatty acid chain was also attached, further enhancing albumin binding and dramatically extending how long the drug circulates. These seemingly small molecular changes were the difference between a daily shot and a weekly one.
In 2024, the Lasker~DeBakey Clinical Medical Research Award, one of the most prestigious prizes in medicine, recognized Joel Habener, Svetlana Mojsov, and Lotte Knudsen for their essential roles in making GLP-1 drugs possible.
Proving It Worked: The SUSTAIN Trials
Semaglutide entered a massive clinical trial program called SUSTAIN, which tested the drug across seven major studies in people with type 2 diabetes. The results were consistent: semaglutide delivered better blood sugar control and more weight loss than every comparator it was tested against.
One trial in the series, SUSTAIN 6, enrolled patients at high cardiovascular risk and found that semaglutide reduced the occurrence of major cardiovascular events by 26% compared to placebo. This was significant because heart disease is the leading cause of death in people with type 2 diabetes, and many older diabetes drugs had no cardiovascular benefit or even increased risk. On the strength of these results, the FDA approved semaglutide as Ozempic on December 5, 2017, for the treatment of type 2 diabetes.
The Unexpected Pivot to Weight Loss
Weight loss had been observed as a side effect in every diabetes trial of GLP-1 drugs. GLP-1 receptors exist not only in the pancreas but also in areas of the brain that regulate appetite and satiety. When semaglutide activates these receptors, people feel full sooner and think about food less often. Novo Nordisk decided to test whether a higher dose of semaglutide could work as a dedicated obesity treatment.
The STEP trial program enrolled thousands of people with overweight or obesity, most of whom did not have diabetes. The results were striking. Across STEP 1, 3, 4, and 8, participants taking semaglutide at the higher 2.4 mg dose lost an average of 14.9% to 17.4% of their body weight over 68 weeks. Between 69% and 79% of participants lost at least 10% of their weight, and 51% to 64% lost at least 15%. In STEP 5, which ran for two full years, average weight loss reached 15.2%.
People with type 2 diabetes lost somewhat less weight, around 9.6% in STEP 2, likely because the metabolic dynamics of diabetes make weight loss harder. In an East Asian population studied in STEP 6, weight loss averaged 13.2% at the higher dose. By comparison, placebo groups in all trials typically lost only 2% to 3%.
These numbers represented a sea change. No previous prescription weight loss medication had come close to producing this level of sustained weight loss outside of surgery. On June 4, 2021, the FDA approved semaglutide at the higher dose under the brand name Wegovy for chronic weight management. The same molecule, discovered through diabetes research, had become the most effective obesity drug ever approved.
Where Ozempic Stands Now
The American Diabetes Association’s 2024 guidelines now list GLP-1 receptor agonists as preferred pharmacotherapy for obesity management in people with diabetes. They also recommend GLP-1 drugs as an option preferred over insulin for glycemic management in many patients, a notable shift in treatment hierarchy. For patients who are already on insulin, guidelines now advise reassessing insulin dosing when a GLP-1 drug is added or its dose is increased, since the combination can lower blood sugar more than expected.
Novo Nordisk’s primary patents on semaglutide are set to expire in March 2026, with data protection ending in January of that year. This timeline means generic and biosimilar versions could begin entering the market in the coming years, potentially expanding access to a drug that has been dogged by shortages and high out-of-pocket costs since its surge in popularity.
The full arc, from an unnamed peptide fragment hidden in the glucagon gene to a drug taken by millions, spans roughly 40 years. It required basic biochemists who weren’t thinking about obesity, pharmaceutical chemists who spent a decade tweaking fatty acid chains, and clinical trialists willing to test a diabetes drug at higher doses in a completely different patient population. Ozempic wasn’t discovered in a single eureka moment. It was built, one molecular modification at a time.