In 1984, Dr. Daniel Drucker, an endocrinologist at the University of Toronto, discovered a hormone in the human gut that helped pave the way for popular diabetes drugs like Novo Nordisks Ozempic and Wegovy.
It’s called a glucagon-like peptide (GLP-1) and its function is to regulate blood sugar levels and suppress appetite.
“The early discoveries we made about 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 amazing to see as a doctor.”
Drucker, along with other members of 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 disappears rapidly from the human body, posing challenges for drug development.
This is where the Gila monster comes into play, the largest lizard in North America.
Gila monsters are also known for their ability to survive long periods without food and their remarkable metabolic adaptations, which have attracted scientific interest in studying blood sugar regulation and developing diabetes drugs.
This venomous reptile, native to the southern United States, possesses the remarkable ability to go long periods without food. It can effectively slow down your metabolism and maintain stable blood sugar levels without affecting your health. Hormones in this reptile’s venom had also previously been shown to regulate blood sugar.
Drucker wanted to know why and refined his research using the venom of the Gila monster.
“Silver bullet to fight diabetes”
In the mid-1990s, with the help of professional reptile breeder Bob Murphy, the senior curator of herpetology at the Royal Ontario Museum, Drucker’s team tracked down the Gila monster in Utah.
“In the ’90s there were no gene banks, you couldn’t look things up online and you actually had to clone stuff and to do that we had to get lizard DNA,” Drucker said.
“We tried using lizard DNA that was in the Toronto freezer at the Royal Ontario Museum and cloning didn’t work. And so our next step was trying to get a live lizard and obviously these are hard to get, you can’t go into a pet store in Toronto and order these things.
Murphy then contacted the Utah Zoo, known for its expertise in breeding lizards, asking about the possibility of obtaining one for research.
“I called the zoo and said, ‘Hey, there might be the silver bullet to address diabetes,’ and they came back and said yes.”
The Gila monster was flown to Toronto’s Pearson Airport, and Murphy picked up the lizard, adding that while it’s venomous, it had “handled much more dangerous things.”
“It was shipped in a wire cage because they are notorious for digging. And I took him out of the cage and pinned him to the table so I could grab him behind the head so I could put him down using animal protocols,” Murphy said.
After experimenting on the lizard, Drucker and his team found that these reptiles are “very unique in that they have genes for Exendin-4, the protein that has become the first GLP-1 diabetes treatment,” he explained.
The hormone in lizard venom, called Exendin-4, shares structural similarities with the human hormone GLP-1. But unlike GLP-1, it doesn’t break down quickly, meaning it stays active in the body for a long time, making it a perfect candidate for a diabetes drug.
It all depends on 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 of once-a-day treatments or once-a-week treatments,” she said.
The Gila monster hormone was then exploited and synthesized into a pharmaceutical drug. But this 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 drug similar to GLP-1, this lizard venom peptide became the first approved for the treatment of type 2 diabetes anywhere in the world and was approved on April 28 2005, Drucker said.
Subsequently, a new generation of GLP-based drugs emerged that lasted even longer.
The most popular example of these advances is Ozempic, a GLP-based drug that has surpassed its predecessors.
Ozempic works by mimicking the hormone GLP-1. It lowers blood sugar and slows digestion, so people feel full longer.
Drucker said he believes Ozempic is a great tool for treating obesity and type 2 diabetes. He has consulted with Novo Nordisk, the maker of Ozempic, to provide guidance on its development.
In an email to Global News, a Novo Nordisk spokesperson said Drucker’s research provided the basis for understanding GLP-1 receptor agonists, to be developed as drug therapies for the treatment of type 2 diabetes.
“Dr. Druckers’ research is cited in the publication outlining the discovery of semaglutide once a week (Ozempic),” the spokesperson said.
Because there is a shortage of Ozempic, he said he believed it should be used for people with health concerns and not for “casual weight loss.”
Ozempic costs between $200 and $300 a month in Canada. According to the Novo NordisksOzempicinformation website, the most common side effects include nausea, vomiting, diarrhea, constipation, and abdominal pain.
Drucker said that although he discovered GLP-1, which is used in Ozempic, he does not receive any royalties as the patent has long since 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 laboratory at the University of Toronto. And Drucker’s work in the 1980s and 1990s helped pave the way for key diabetes drugs, such as Ozempic.
“It’s all fundamental, very important and a major contribution to science,” he said. “He’s been really instrumental in the development of this area. So Canada can take great credit for that.
Drucker’s decade-long research into GLP-1 drugs in the treatment of diabetes and other metabolic diseases has earned him several awards.
In February, he was awarded Israel’s prestigious Wolf Prize for work on diabetes. In 2021, he was named a 2021 Canada Gairdner International Award recipient. He was inducted into the Canadian Medical Hall of Fame, and in 2015, he was made an Officer of the Order of Canada.
Dr. Daniel Drucker in his laboratory at the University of Toronto.
Daniel Drucker
He acknowledges his contributions to the field, but emphasized that the discovery of these drugs 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 created new and better versions of them. So, it was really a great collective effort from the scientific community based on our initial discovery,” she said.
He added that the scientific community has made significant progress in developing more potent drugs for diabetes and weight loss.
“More recently, we’ve seen even greater weight loss achieved with the drug Tirzepatide,” she said, adding that it’s approved for type 2 diabetes in the United States and Canada and could be approved for people with obesity by the end. of this year.
“This will really change how we can improve the health of people with obesity for years to come,” she said.
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