Drug discovery is a game of long odds: only one in ten thousand lab discoveries survives the gauntlet from benchtop to prescription pad. Stranger still is the fate of a hormone discovered in a deep-sea creature and lizard venom, now reborn in the age of social media as a global weight loss icon – something it was never intended to be. This is the story of Ozempic, written in part by Dr. Daniel Drucker, a Toronto scientist whose work helped bring the drug to life. Before we delve in, we must pay tribute to University of Toronto scientists Frederick Banking and Charles Best, who began the first few pages of this story, with a note on diabetes.
Diabetes, the incretin effect, and glucagon
Diabetes comes in two forms, both characterized by elevated blood sugar (glucose) levels but differing in etiology. Both varieties revolve around the insulin hormone, a chemical messenger secreted into the bloodstream that regulates glucose uptake by cells. In type 1 diabetes, insulin-producing pancreatic b-cells are destroyed by the body’s immune system. In type 2 diabetes (T2D), the pancreas still makes insulin, but the body resists the hormone’s command to absorb glucose, forcing the pancreas to produce more and more until it, too, begins to fail.
By the 1960s, physicians faced an epidemic of patients with T2D and few tools to help them. Researchers began searching for ways to coax the pancreas into properly absorbing glucose. Whilst doing so, they stumbled upon a curious fact: when patients ingested glucose, their bodies released more insulin and lowered blood sugar levels more effectively than when the same amount of glucose was infused directly into their veins. This suggested that the gut was communicating with the pancreas to stimulate insulin secretion in response to food. Today, this is known as the incretin effect. Scientists began testing hormones to see if they could reproduce this effect. One pancreatic hormone stood out. Glucagon, long cast as insulin’s nemesis for its role in raising blood sugar, behaved strangely. Counterintuitively, injecting glucagon triggered a spike in insulin before blood glucose levels even rose. This paradox, that a hormone famed for undoing insulin’s work might also help summon it, transformed glucagon from villain to muse. Despite stimulating insulin release, the ultimate increase in blood glucose following glucagon administration meant it was not a suitable therapy. This, however, begged the question: is there something like glucagon that triggers insulin secretion without raising blood sugars? To answer this, researchers had to first embark on a deep dive to understand glucagon.
Angler fish and the discovery of glucagon-like peptide 1
In the early 1980s, isolating pancreatic hormones from mammals remained a challenge, posing a bottleneck for investigative studies. Scientist Joel Habener turned to the abyssal anglerfish as an alternative model organism, whose distinct pancreatic structure made it easier to isolate its hormones. Upon successfully isolating glucagon from the anglerfish, Habener’s team discovered that glucagon is derived from a larger precursor protein called preproglucagon, which can be cut into peptides. When scientists later examined the mammalian version of the preproglucagon gene, they found a peptide called glucagon-like peptide 1 (GLP-1).
At first, GLP-1 alone did not stimulate insulin release. However, a member of Habener’s team, Svetlana Mojsov, noticed that when pancreatic GLP-1 is shortened in its length, it looks more like glucagon and acts as a powerful trigger for insulin secretion in mammals. Building on this discovery, Daniel Drucker showed that the shortened version of pancreatic GLP-1 naturally exists at high levels in the small intestine. This observation by Drucker cemented the role of shortened GLP-1 as an incretin hormone. Importantly, GLP-1 only worked when blood glucose levels were high, reducing the risk of hypoglycemia – a condition characterized dangerously low blood sugar levels which is a common complication of other diabetes medication. This made the peptide ideal for patients with type 2 diabetes. Intravenous infusions of GLP-1confirmed its effect in humans, but its half-life – the amount of time it takes for the body to eliminate half of the original dose – was only about two minutes, too short to be useful as a drug.
The Gila monster and exendin-4
A potential solution was to find an alternative that was stable enough to stay longer in the body. Endocrinologist John Eng turned to an unlikely source: the venom of the Gila monster, a desert-dwelling lizard whose bite was known to overstimulate the pancreas. From this reptile, Eng isolated a peptide called exendin-4, which bore striking resemblance to shortened form of GLP-1. When administered to dogs, exendin-4 boosted insulin secretion and normalized blood glucose levels. Importantly, exendin-4 stayed in the bloodstream for hours instead of minutes, making it a viable drug candidate.
Pharma and serendipity
Following his successful experiments, Eng filed a patent for exendin-4 and licensed it to Amylin Pharmaceuticals, which launched clinical trials in patients with type 2 diabetes. These trials showed that patients treated with exendin-4 had significantly lowered blood glucose levels compared to those on placebo controls. Building on this success, a research team led by Lotte Bjerre Knudsen at Novo Nordisk experimented with modifying the structure of GLP-1. This modification increased the peptide’s stability and longevity, making once-daily injections of this drug feasible. At the highest doses of this modified GLP-1, patients lost around 3% of their body weight, a serendipitous discovery prompting efforts to further optimize the molecule. Through a series of tweaks, scientists eventually created semaglutide, a next-generation GLP-1 that strikingly led to 15-20% weight loss in patients during clinical trials. This breakthrough compound is now known by its globally recognized trade name: Ozempic.
The world of Ozempic
Few drugs have leapt from medical journals to late-night television quite like Ozempic. What began as a treatment for T2D has become a global phenomenon: hailed, debated, and meme-ified in equal measure. Demand outpaced supply as people sought prescriptions for cosmetic weight loss, sparking shortages for diabetic patients and ethical debates about who these drugs are truly for. Physicians were left balancing excitement with caution, reminding the public that while GLP-1 variants are powerful tools, they are not magic. They work best when treating disease, not vanity.
What’s next?
Meanwhile, science continues to evolve. Variations of GLP-1 have shown promise far beyond treating diabetes and obesity, with studies suggesting therapeutic benefits for heart failure and chronic kidney disease. Many of these insights are rooted in the work from Dr. Daniel Drucker’s group at the University of Toronto, whose research continues to illuminate how these hormones act across multiple organ systems. Today, his lab is exploring how GLP-1–based therapies might modulate substance use disorders and neurodegenerative diseases, which could once again expand the boundaries of what this remarkable class of molecules can do.
From angler fish to lizard venom to once-weekly injection that reshaped modern medicine, the story of Ozempic is as unlikely as it is profound. A century after Banting and Best discovered insulin in Toronto, another hormone has emerged from this city’s labs and is redefining how we think about metabolism, appetite, and chronic disease. What began as a search to help people with diabetes now sits at the intersection of biology, business, and culture. This serves as a reminder that scientific discovery often takes the most unexpected paths.
Yashar Aghazadeh Habashi
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- The Story of Ozempic - January 25, 2026
