It was 1984. Newly arrived at Harvard Medical School for a research fellowship, Drucker planned to study thyroid disease – an interest he had developed as a University of Toronto medical student and later as a resident at Toronto General Hospital.
Instead, his supervisor, Joel Habener, delivered unexpected news: the lab was phasing out its thyroid program. Drucker would be studying glucagon, a hormone that regulates blood sugar.
“I was very clear I was going to be a thyroid clinician,” recalls Drucker – now a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health and a University Professor of medicine in U of T’s Temerty Faculty of Medicine. “The fact that I ended up working on these peptide hormones that had nothing to do with the thyroid was disappointing.”
Yet the change proved pivotal.
Within years, Drucker would help identify and characterize glucagon-like peptide-1 (GLP-1) – a hormone produced in the gut that stimulates insulin release and curbs appetite. This work laid the scientific foundation for blockbuster drugs such as Ozempic, approved for treating type 2 diabetes (and widely used for weight loss), and Wegovy, approved for weight loss.
The medications have rapidly become household names – generating headlines, social media buzz and fodder for talk show hosts.
Less widely discussed is the growing evidence that GLP-1-based therapies may help treat a wide array of other conditions, from kidney disease to neurological disorders.
These advances have earned Drucker a growing list of honours, including the Canada Gairdner International Award and recognition on Time magazine’s list of the world’s 100 most influential people. Last year, Drucker, Habener and three international collaborators received the Breakthrough Prize in Life Sciences – often described as the “Oscars of Science” for “the discovery and characterization of GLP-1 and revealing its physiology and potential in treating diabetes and obesity.”
For Drucker, however, the most meaningful reward is seeing how his fundamental research, driven by curiosity, has resulted in game-changing treatments that are now helping millions of people.
“Nobody set out in the GLP-1 field 25 or 30 years ago to invent a drug that produced weight loss or would reduce heart disease, liver disease or kidney disease,” says Drucker, who holds the Banting and Best Diabetes Centre-Novo Nordisk Chair in Incretin Biology. “This all came about from basic science observations that were unexpected but thankfully translated into clinical findings of use for patients with these challenging disorders.”
A HORMONE WITH PROMISE
The breakthroughs did not come quickly. It took decades of painstaking work for Drucker’s early laboratory findings to evolve into widely used treatments.
In 1987, he returned to U of T as an assistant professor at the Banting and Best Diabetes Centre. By this time, Drucker had become the first to identify the biologically active form of GLP-1 and to show, in insulin-producing cells grown in a dish, that GLP-1 boosts insulin secretion when glucose levels are high – but not when they’re low.
Yet GLP-1 had a major drawback: it degraded rapidly in the human body. Any therapy based directly on the hormone would be short-lived.
The solution came from an unlikely source – the Gila monster, a desert reptile whose venom contains a hormone that stimulates insulin release but is more stable than human GLP-1.
With help from the Royal Ontario Museum, Drucker obtained a Gila monster and analyzed its venom. He discovered that the reptile’s hormone could activate the human GLP-1 receptor, even though it was structurally distinct from the human body’s own GLP-1. His lab published the findings in 1997, helping to set the stage for drug development.
Years of further research and industry collaboration followed. In 2005, a synthetic version of the reptilian hormone became the first GLP-1 drug approved for type 2 diabetes, administered by a twice-daily injection. (Today’s medications offer longer-lasting, once-weekly dosing).
By then, Drucker’s lab had also helped establish that GLP-1 acted on receptors in the brain to suppress appetite, making these receptors a viable target for obesity treatment. (Prior research by other scientists had shown GLP-1 also curbed appetite by slowing gastric emptying.) This led to the approval of the first GLP-1 drug for weight loss in 2014.
TREATING CHRONIC CONDITIONS
With GLP-1 weight-loss drugs now surging in popularity, Drucker says he is concerned about how celebrity culture and social media hype could affect public perception and usage. At the same time, he hopes growing awareness of their effectiveness can help combat the stigma that obesity stems from a lack of discipline.
“People have struggled for years despite doing everything we tell them: the traditional advice of eat less and move more is just not helpful for many. Now, we see spectacular improvements in their health,” says Drucker. “It’s tremendously satisfying, and it allows many of these individuals to turn to the doubters in society and say, ‘I just needed help – and the GLP-1 medicines were the help that I needed.’”
Meanwhile, clinical evidence continues to expand. GLP-1 drugs are now used to reduce cardiovascular risk, kidney disease, metabolic liver disease and sleep apnea – owing to their effects on metabolism, inflammation and insulin sensitivity.
The hormone is also produced in the brain, says Drucker, where it appears to have protective properties. Clinical trials are underway to evaluate GLP-1 drugs for neurodegenerative diseases. Researchers have observed that they can dampen reward-seeking behaviour, raising the possibility that the drugs could one day play a role in treating substance use disorders.
As the list of potential benefits of GLP-1 grows, Drucker warns that the buzz must be balanced with caution and scientific rigour.
“There’s a tendency to say GLP-1 is a wonder drug, but it’s not going to help all of these disorders. We have to prepare to be disappointed,” he says. “But we’re very lucky that there are so many clinical trials underway that will tell us when GLP-1 is useful and when it’s not. It’s going to be an exciting next couple of years.”
Drucker’s current research extends beyond GLP-1. His lab has also discovered the role of a related hormone, GLP-2, in stimulating intestinal growth – work that led to a breakthrough treatment for short bowel syndrome, a rare and debilitating condition in which patients can’t absorb sufficient nutrients due to missing or damaged intestine.
Today, his focus remains on understanding how GLP-1 improves brain health and reduces inflammation across a range of diseases, while mentoring the next generation of researchers who will push the field forward.
He credits U of T’s research ecosystem as central to that work.
“I have experts in almost every endeavour working across the street from me at U of T and hospital research institutes,” he says. “It’s an extremely rich environment full of scientific talent, with people who are friendly and approachable and can elevate what we do.
“That’s why I’ve never left. I don’t think I could do what I do easily in other places. This has been a fantastic scientific home for me.”
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