White Coat Black Art26:30Ozempic: The good, the bad and the future
Despite widely publicized reports of rare but severe side effects, obesity doctors say Ozempic and drugs like it have the potential to improve medical help for a chronic illness that patients have been forced for too long to try to cure on their own.
“There are still some aspects of our health-care community that say, ‘this is not important, weight loss is not important; it’s just cosmetic and you’re really not improving the health of these people,'” said Dr. Daniel Drucker, a physician-scientist whose research helped pave the way for Ozempic, one of several brand names for a drug known as semaglutide. “But now I think that argument will be laid to rest.”
Ozempic and other drugs in its class are known as glucagon-like peptides, or GLPs. Because GLPs act to stimulate insulin secretion, the first was approved for use as a diabetes drug in 2005, said Drucker, who is a senior scientist at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto.
But it was actually back in the late 1990s that Drucker’s lab, as well as that of Dr. Steve Bloom in the U.K., began to publish what they’d observed in clinical trials — that patients treated with GLP medicines for their diabetes were also losing weight.
Now new data shows that semaglutide also reduces rates of heart attacks, strokes and death in people with pre-existing cardiovascular conditions, something Drucker told White Coat, Black Art host Dr. Brian Goldman he believes will “change the conversation around the importance of treating people with obesity.”
‘Not feeling hungry all the time’
Michael Morris, 58, says he’s been wrestling with his weight since he was a teenager.
“I’ve always gone up and down, yo-yo, every diet,” he said. When he needed a CPAP machine for sleep apnea about 18 months ago, he ended up in a program that supported him through some dietary changes to help address the apnea, along with his high blood pressure and cholesterol levels, and pre-diabetic blood sugar status. When Morris met with a doctor, he asked about Ozempic, and the two agreed he could give it a try.
Since then, Morris said he has gradually lost around 40 pounds and seen improvements in his other conditions as well.
“It’s like it changes … the way you think about food, like I’m not feeling hungry or ravenous all the time,” he said.
Before Ozempic, Morris said he could never tell when he was full.
“I know that’s probably hard for people to understand. I would eat stuff and then I would just keep eating, and then I got to the point where it made me feel sick. And then I’d be like, ‘Oh, I’m not doing that again.’
“I guess food, it’s like an addiction for me. And if you’re an alcoholic, people don’t say, ‘Oh, I’m just trying not to drink.’ There are programs and stuff.”
The genetic component
Dr. Sasha High, an internal medicine and obesity physician who works in private practice in Toronto, says it’s important to understand that not everyone experiences food in the same way.
“We know that 50 to 70 per cent of obesity is genetically determined and the genes involved are central nervous system genes, that means genes that control factors with our brain,” she said. These affect the way the brain responds to the food that’s around us, whether we have cravings for sugar or salty foods and whether we enjoy exercise. “All of that is kind of determined by our physiology.”
That doesn’t mean weight is set in stone, said High, but it does mean there’s a range of what your body shape is going to look like, determined by your genetics and then by lifestyle choices.
When she started working in the area of obesity back in 2012, High said there wasn’t much doctors could offer beyond telling patients to eat less, exercise more and count calories.
That message is disempowering for people who have contended with obesity for a long time, she said.
“The issue is not that they don’t understand that they need to do that. The issue is that life gets in the way and stressers come and we eat because we are bored and we eat because we’re sad and we eat because it’s 9:00 at night and we’ve had a stressful day.”
Drucker said GLP medications work in two ways to tell patients that they’re not hungry. First, they tell the brain to physically slow the emptying of the stomach, and second, they affect the brain’s hunger signals, suppressing appetite.
Some of Drucker’s research was done in partnership with companies that produce or are working on weight-loss drugs, including Pfizer and Novo Nordisk.
On Nov. 11, the New England Journal of Medicine reported the results of a study on the safety of semaglutide in people with obesity who also had cardiovascular disease, said Drucker. On average, the patients received either semaglutide or a placebo for 34 months.
“It showed not only weight loss but reduced rates of heart attacks, strokes and death.”
However, some patients have experienced serious side effects, including stomach paralysis and malnutrition.
Pamela Cole is one of those patients. The 38-year-old from Marmora, Ont., initially responded well to the medication. But when her doctor increased her dose about eight months in, she started to get flu-like symptoms that escalated from there.
“I continued to get worse to the point I couldn’t eat anything without severe stomach pain,” said Cole. She wound up visiting the hospital four or five times in the space of two weeks, she said.
During the last of those visits, she was treated for severely low potassium levels that were impacting her kidney and liver function. A specialist eventually advised her to discontinue Ozempic, and after doing so, her symptoms resolved.
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In a statement, Ozempic manufacturer Novo Nordisk told CBC it stands behind the safety and efficacy of all of its GLP-1 medicines when used by appropriate patients consistent with the product labelling and approved indications.
Drucker said Cole’s experience is atypical next to research findings from eight large cardiovascular safety trials — some with more than 10,000 subjects — that ran over periods of two to six years.
“And what we see generally are favourable results. In those trials, we see a reduction in heart attacks, strokes, cardiovascular death … and we do not see an increase in cancer or an increase in pancreatitis,” he said.
However, he said it’s important to be cautious.
“With the newer, more powerful medicines and the expanding patient population, there is always the possibility to see something that we haven’t before.”
Dr. Nav Persaud, a family medicine physician at St. Michael’s Hospital in Toronto, told CBC in January that it wouldn’t be the first time the side effects of a weight-loss drug turned out to be more serious than anticipated.
“We have seen it happen many times where there were these heralded wonder drugs that turned out not to work or to harm and kill people,” he said.
In France, a diet drug called Mediator that started as a Type 2 diabetes treatment was taken off the market in 2009 after being blamed for thousands of deaths due to heart-valve problems.
Dr. Sean Wharton is an internal medicine specialist at Michael Garron Hospital in Toronto and assistant professor at the University of Toronto who researches obesity medicine. He likens the difficulty people face accessing medical help for obesity to the experience many people with mental health issues have with expectations that they should “just be happier.”
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However, until weight-loss medicines become a lot more accessible, he said he doesn’t see them making a big dent in the obesity epidemic. Ozempic has been in short supply since its popularity skyrocketed — more than 3.5 million prescriptions were filled at Canadian pharmacies last year The very nature of an injectable drug that’s expensive to manufacture, ship and store means only people with the financial resources or particularly good drug plans can get their hands on it, said Wharton, who has done paid research for Novo Nordisk.
In September, the New England Journal of Medicine published Wharton’s phase-two trial data showing that a once-a-day pill called orforglipron resulted in a weight reduction of at least 10 per cent after 36 weeks in 46 to 75 per cent of participants.
Drucker said that GLP medicines won’t erase the need to address access to healthy, affordable foods, to design cities that are easier to navigate on foot or bicycle, or to promote healthy habits around diet or exercise.
“But if you’re sitting across the desk from someone who is living with obesity and they have a higher risk of heart disease and kidney disease and liver disease and cancer, you know, I think GLP medicines are a very useful option.”