Daniel Drucker's path to a discovery that would transform millions of lives began not with a breakthrough - but a setback.
He had just arrived at Harvard Medical School in 1984 for a research fellowship, intending to focus on thyroid disease - an area he became interested in as a University of Toronto medical student and, later, as a fellow and resident at Toronto General Hospital.
His supervisor, Joel Habener , delivered the bad news: the lab was phasing out its thyroid program. Instead, Drucker would be tasked with studying glucagon, a hormone that regulates blood sugar.
"I was very clear that I was going to be a thyroid clinician, so the fact that I ended up working on these peptide hormones that had nothing to do with the thyroid … that was disappointing," says 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.
It would prove to be a pivotal moment.
His new research direction would aid in the discovery of glucagon-like peptide-1 (GLP-1) in the human body, a hormone that stimulates insulin release and promotes weight loss - ultimately paving the way for blockbuster drugs such as Ozempic, approved for treating type 2 diabetes (but also used for weight loss), and Wegovy, approved for weight loss. Both have rapidly become household names - not to mention fodder for the media and late-night talk show hosts.
What's less talked about outside research circles is how GLP-1 therapies are also showing huge promise in treating a wide array of other conditions, from kidney disease to neurological disorders.
These advances have earned Drucker a growing list of awards and accolades , including the Canada Gairdner International Award and a spot on Time magazine's list of 100 most influential people . Earlier this year, Drucker, Habener and their collaborators - Jens Juul Holst of the University of Copenhagen, Svetlana Mojsov of Rockefeller University and Lotte Bjerre Knudsen, chief scientific advisor at Novo Nordisk - were recognized with the Breakthrough Prize in life sciences for "the discovery and characterization of GLP-1 and revealing its physiology and potential in treating diabetes and obesity."
But he says the biggest 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."
The breakthroughs didn't happen immediately. It took decades of painstaking work for Drucker's early research to result in tangible treatments.
In 1987, Drucker returned to U of T as an assistant professor at the Banting and Best Diabetes Centre. By that time, researchers had learned that GLP-1 triggered insulin secretion when blood sugar levels are high, suggesting its potential as a type 2 diabetes treatment.
Yet, GLP-1 still had a major drawback: it degraded rapidly in the human body.
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, analyzed its venom, and discovered that its version of the hormone was active at the GLP-1 receptor, yet distinct from lizard GLP-1. His lab published the findings in 1997 .
Years of industry research followed and, in 2005, a synthetic version of the reptilian hormone became the first GLP-1 drug approved for type 2 diabetes via 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 specific receptors in the brain to suppress appetite , making the receptors a viable target for obesity treatment. (Prior research by other scientists had shown GLP-1 also curbed appetite by slowing gastric emptying.) That led to the first GLP-1 drug for weight loss being approved in 2014.
With GLP-1 weight-loss drugs now surging in popularity, Drucker expresses concern about the impact of celebrity culture and social media hype on how the medications are used. 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.'"
GLP-1 drugs are now also being used to curb cardiovascular risk, kidney disease, metabolic liver disease and sleep apnea - thanks to their impact on metabolism, inflammation and insulin sensitivity.
GLP-1 is also produced in the brain, says Drucker, where it appears to have neuroprotective effects. Clinical trials are now exploring GLP-1 drugs for Alzheimer's and Parkinson's. The hormone even reduces reward-seeking behaviour, making it promising for 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 is focused on understanding GLP-1's role in improving brain health and reducing inflammation across diseases. He has also discovered the role of a related hormone, GLP-2, in stimulating intestinal growth, leading to a breakthrough treatment for short bowel syndrome - a rare and debilitating condition in which the body can't absorb nutrients due to missing or damaged intestine.
He says he's focused on day-to-day science and mentoring the next generation of researchers as GLP-1 science enters a new era - and that U of T is an ideal place to carry out the work.
"I have experts in almost every endeavour working across the street from me at the University of Toronto campus 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, and this has been a fantastic scientific home for me."
