In 1984, Dr. Daniel Drucker, an endocrinologist from the University of Toronto, discovered a hormone in the human gut that helped pave the way for popular diabetes drugs such as Novo Nordisk’s Ozempic and Wegovy.
It’s called glucagon-like peptide (GLP-1) and its function is to regulate blood sugar levels and suppresses appetite.
“The first discoveries we made for what GLP-1 did naturally supported the development of treatments for diabetes,” Drucker told Global News. “I did basic science. I really had no idea where this would lead. And now it’s having a huge clinical impact globally, which is just great to see as a physician.”
Drucker, along with others in the scientific community, wanted to turn GLP-1 into a drug to help people manage Type 2 diabetes. However, there was a problem: GLP-1 quickly disappears from the human body, positing difficulties in drug development.
Here enters the Gila monster, the largest lizard in North America.
This venomous reptile, native to the southern U.S., possesses the remarkable ability to endure extended periods without food. It can effectively slow down its metabolism and sustain stable blood sugar levels without compromising its health. Hormones in this reptile’s venom had also previously been shown to regulate blood sugar.
Drucker wanted to know why and honed his research using venom from the Gila Monster.
‘Silver bullet for dealing with diabetes’
In the mid-1990s, with the help of a professional reptile handler Bob Murphy, the senior curator of herpetology at the Royal Ontario Museum, Drucker’s team tracked down the Gila monster in Utah.
“In the 1990s there were no gene banks, you couldn’t look stuff up online and you actually had to clone stuff and in order to do that we had to get lizard DNA,” Drucker said.
“We tried using lizard DNA that was in the freezer in Toronto at the Royal Ontario Museum and the cloning didn’t work. And so our next step was to try and get a live lizard and obviously these are difficult to obtain, you can’t walk into a pet store in Toronto and order these things.”
Murphy then contacted the Utah Zoo, known for its expertise in lizard breeding, asking about the possibility of getting one for research.
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“I put out the call to the zoo and said, ‘Hey, there may be the silver bullet for dealing with diabetes’ and they came back and said yes.”
The Gila monster was flown into Toronto Pearson Airport and Murphy picked up the lizard, adding that although it is venomous, he had “handled things far more dangerous.”
“It was shipped in a wire cage because they are notorious for digging. And I took it out of the cage, and I pinned it on the table so I could grab it behind the head so we could euthanize it using animal protocols,” Murphy said.
After experimenting on the lizard, Drucker and his team found that these reptiles are “very unique in that it has genes for Exendin-4, the protein that became the first diabetes GLP-1 treatment,” he explained.
From venom to Ozempic
The hormone in the lizard venom, called Exendin-4, shares structural similarities with the human hormone GLP-1. But unlike, GLP-1, it does not quickly break down, meaning it remains active in the body for an extended period, making it a perfect candidate for a diabetes drug.
It’s all about how long these treatments last in the body, explained Dr. Ehud Ur, an endocrinologist at St. Paul’s Hospital and Vancouver General Hospital.
“That’s really the whole trick around once-a-day treatments or once-a-week treatments,” he said.
The Gila monster hormone was then harnessed and synthesized into a pharmaceutical drug. But this one was done by a biochemist south of the border, Dr. John Eng, who patented the lizard venom peptide. He called it Exenatide.
“Despite all the pharmaceutical companies in the world trying to develop a GLP-1-like drug, this lizard venom peptide became the first approved for the treatment of Type 2 diabetes anywhere in the world, and it was approved on April 28th, 2005,” Drucker said.
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Subsequently, a new generation of GLP-based drugs emerged that lasted even longer.
The most popular example of these advancements is Ozempic, a GLP-based drug that surpassed its predecessors.
Ozempic works by mimicking the GLP-1 hormone. It lowers blood sugar and slows down digestion, so people feel full longer.
Drucker said he believes Ozempic is a great tool to treat obesity and Type 2 diabetes. In fact, he has consulted with Novo Nordisk, the manufacturer of Ozempic, to provide guidance on its development.
In an email to Global News, a spokesperson from Novo Nordisk said Drucker’s research provided the basis for understanding GLP-1 receptor agonists, to be developed as pharmacologic therapies for the treatment of Type 2 diabetes.
“Dr. Drucker’s research is cited in the publication outlining the discovery of once-weekly semaglutide (Ozempic),” the spokesperson said.
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Because there is a short supply of Ozempic, he said he believes it should be used for people with health problems, and not for “casual weight loss.”
Ozempic costs between $200 and $300 per month in Canada. According to Novo Nordisk’s Ozempic information website, the most common side effects include nausea, vomiting, diarrhea, constipation and abdominal pain.
Drucker said although he discovered GLP-1, which is used in Ozempic, he does not receive any royalties as the patent has long expired.
‘Very important’ and ‘critical’ contribution
Canada has played a major role in the area of diabetes treatment, Ur said.
In 1921, insulin was discovered by a team of scientists in a lab at the University of Toronto. And Drucker’s work in the 1980s and 1990s helped pave the way for key diabetes drugs, like Ozempic.
“It’s all critical, very important and a major contribution to the science,” he said. “It’s been really instrumental in the development of this area. So Canada can take great credit for it.”
Drucker’s decades-long research into the field of GLP-1 drugs in treating diabetes and other metabolic diseases has landed him several awards.
In February, he was awarded Israel’s prestigious Wolf Prize for work on diabetes. In 2021, he was named a laureate of the 2021 Canada Gairdner International Award. He was inducted into the Canadian Medical Hall of Fame, and in 2015 he was appointed Officer of the Order of Canada.
He acknowledges his contribution to the field but stressed the discovery of these medications was done as a community.
“Certainly, we were among the first to make that discovery. But tens of thousands of people have studied these proteins and made new and better versions. So, it’s really been a large collective effort from the scientific community based on our initial discovery,” he said.
He added that the scientific community has made significant advancements in the development of more potent medications for diabetes and weight loss.
“More recently, we’ve seen even more weight loss obtained with the drug Tirzepatide,” he said, adding that it’s approved for Type 2 diabetes in the U.S. and Canada and may be approved for people with obesity by the end of this year.
“This is really going to change how we can improve the health of people with obesity in the years to come,” he said.
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