Cardiac Surgeon-Scientist Dr. Subodh Verma, left, and his patient Richard Neilson at St. Michael's Hospital on Jan. 3. When Neilson suffered a heart attack in 2019, Dr. Verma performed a double bypass surgery on Neilson’s heart, operating on Christmas Day.Sammy Kogan/The Globe and Mail
Shortly after Richard Neilson survived a heart attack and double bypass surgery in 2019, his cardiac surgeon invited him to join a clinical trial for a medication that researchers hoped would cut his risk for future heart attacks.
The drug was semaglutide, now famous as Ozempic, the blockbuster Type 2 diabetes treatment that has become a medical and cultural phenomenon because of how readily it helps people lose weight.
Mr. Neilson, a 68-year-old Toronto truck driver, agreed to take part in the trial for the potential cardiovascular benefits, not because he cared much about his figure, although he did manage to drop 45 pounds from his six-foot-one frame in about a year while taking Wegovy. The higher-dose version of semaglutide is marketed for weight management and manufactured by the same company as Ozempic.
“If it was just a weight-loss thing,” Mr. Neilson said, “I wouldn’t have even bothered.”
The clinical trial in which Mr. Neilson participated, called SELECT, paved the way for Health Canada’s decision in November to approve Wegovy to reduce the risk of heart attacks – the first time the Canadian regulator greenlit a version of semaglutide for a condition other than diabetes or overweight and obesity.
Experts say it won’t be the last. The United States Food and Drug Administration approved a similar drug, tirzepatide, sold as Zepbound, for obstructive sleep apnea just before Christmas. Semaglutide, tirzepatide, and other drugs that belong to a class known as glucagon-like peptide-1 (GLP-1) receptor agonists are being tested for dozens of other chronic conditions, including chronic kidney, non-alcoholic fatty liver, Alzheimer’s and Parkinson’s diseases.
The new and potential future uses for GLP-1 drugs pose a challenge for cash-strapped public drug plans in Canada, which have so far limited coverage of Ozempic to people with diabetes. They have declined to cover Wegovy because it’s marketed as a weight-management drug. That could change if Wegovy and its cousins, including tirzepatide, are authorized and pitched for other chronic illnesses that afflict millions of overweight and obese Canadians.
“This would be a massive shift,” said Mina Tadrous, a University of Toronto professor who studies pharmaceutical policy and drug safety. Insurers around the world have traditionally balked at paying for weight-loss medications, lumping them in with cosmetic treatments such as Botox. The success of GLP-1 medications is forcing payers to “revisit their paradigms,” he said.
“The thing that’s lagging behind is the true evidence. A lot of it is hypothetical,” Dr. Tadrous cautioned. “The cardiovascular benefit was the first time we saw a signal that it’s not just hypothetical any more.”
GLP-1 drugs manage blood sugar and reduce weight by mimicking the GLP-1 hormone the body produces naturally. The weekly injections slow stomach emptying, but appear to work most powerfully in the brain, where they curb hunger cues. Their main side effects are nausea and gastrointestinal upset.
Some recent analyses of clinical trial data for GLP-1 medications in cardiovascular and kidney disease suggest the drugs could have health benefits independent of weight loss, possibly because they seem to dampen inflammation throughout the body.
“These are all brand-new conversations,” said Daniel Drucker, a clinician-scientist based at the Lunenfeld-Tanenbaum Research Institute at Toronto’s Mount Sinai Hospital and one of the researchers who discovered the GLP-1 hormone. “I raise this point exactly in every lecture: We need to move our thinking from weight loss as the primary goal for everyone. It’s very important, but improving health is the primary goal for many people.”
Ozempic is already far and away the top-selling drug in Canada, according to data that IQVIA, a life-sciences analytics company, provided to The Globe and Mail.
Nearly $2.3-billion worth of Ozempic was sold through Canadian retail pharmacies in the first 11 months of last year, more than twice as much as the next highest seller, Stelara, a treatment for Crohn’s and other autoimmune diseases. (Those figures include markups and dispensing fees.)
The IQVIA data count all payers, including Canadians without diabetes who pay out of pocket to use Ozempic off-label to lose weight. Wegovy, which first became commercially available in Canada last year, recorded nearly $147-million in sales between April and the end of November.
In Canada, a 28-day supply of the weekly injectable Wegovy sells for $388.64 before pharmacy markups and dispensing fees, according to Novo Nordisk, which makes both versions of semaglutide.
Dr. Tadrous and his colleagues published a study last month showing that the dollar value of all drug purchases in Canada, regardless of payer, grew by 13.7 per cent between 2022 and 2023 – an increase that was so much higher than expected that Dr. Tadrous at first thought the summer student who crunched the numbers made a mistake.
“This annual growth,” he said, “is all driven by semaglutide.”
It’s not yet clear how that growth is affecting public drug programs because the Canadian Institute for Health Information’s most recent report on prescribed drug spending only includes data up to the end of 2022. CIHI found that taxpayer spending on diabetes drugs, including GLP-1s, reached $868-million that year, representing 24 per cent of the total growth in public drug program spending nationally.
The biggest driver of that increase was Ozempic, which reached $434-million in public spending in 2022, up from $265-million the year before.
What is clear, according to one Ontario study, is that many patients with diabetes, obesity or heart disease who might benefit from GLP-1 drugs aren’t getting them.
That includes Mr. Neilson. He stopped taking Wegovy about a year and a half ago when the SELECT trial ended because he couldn’t afford the drug on his trucker’s salary. As a senior, he qualifies for Ontario’s Drug Benefit Program, but the plan does not cover Wegovy.
Subodh Verma, the University of Toronto professor of surgery and pharmacology who performed Mr. Neilson’s double bypass surgery in 2019 at St. Michael’s Hospital in Toronto, believes Mr. Neilson would benefit from continuing to inject the drug.
“There is an intrinsic value of the medication that is not necessarily related to weight, that is actually protecting his heart, and I need him to be back on it for that reason,” said Dr. Verma, who led the SELECT trial in Canada and is spearheading clinical trials of other GLP-1 drugs as well. (He and Dr. Drucker have both disclosed receiving honorariums from pharmaceutical companies, including Novo Nordisk, which helped introduce The Globe to a SELECT participant for this story.)
Some drug companies offer trial extensions or bridging programs that cover the cost of medications after a trial ends, but Novo Nordisk has not done so in the case of SELECT, which enrolled more than 17,000 people. The company declined to say why not when asked in writing by The Globe.
“Novo Nordisk is working with federal and provincial governments, insurance providers and employers, as well as patient advocacy organizations to improve access to our medications as well as advocating for recognition of obesity as a chronic disease,” Kate Hanna, senior director of communications for Novo Nordisk Canada, replied by e-mail.
Novo Nordisk’s Canadian advocacy includes resubmitting Wegovy to an expert committee at Canada’s Drug Agency, which advises the public drug plans on covering medications. The CDA’s predecessor agency recommended against reimbursing Wegovy for weight management in 2022, but it may reconsider now that Wegovy has Health Canada approval for cardiovascular disease. The CDA is expected to issue a new recommendation later this year.
“The conversation that needs to happen is that this is for heart protection and not for cosmetic reasons,” Dr. Verma said.
Editor’s note: An earlier version of this story incorrectly said Wegovy was the first GLP-1 receptor agonist to be approved for a condition other than diabetes or overweight or obesity. Two other drugs in the GLP-1 class were previously approved for other indications. This version has been updated.