Since Ozempic and Wegovy crashed into the spotlight early this year, numerous other experimental drugs — and one natural remedy — have been trying to replicate its success.
While the supplement being touted as “Nature’s Ozempic,” berberine, has experts raising their eyebrows, doctors are getting excited about new hormonal treatments for obesity that may be more effective than Ozempic, according to early-stage clinical trials.
Ozempic is approved in Canada as a treatment for type 2 diabetes, though it has garnered headlines for its off-label use as a weight-loss drug. That’s because the medical ingredient in Ozempic, called semaglutide, is the exact same ingredient that makes up Wegovy, a drug specifically approved for obesity treatment.
Wegovy was approved for use in Canada two years ago, yet no one in the country has ever received a Wegovy prescription because of persistent supply problems.
In its absence, doctors have been prescribing Ozempic to treat obese patients — a practice that has received backlash over worries that it would keep the drugs out of the hands of diabetics. Canada is currently experiencing a shortage of the 1 mg dose of Ozempic, as of Aug. 21, which is expected to end in early October.
“Addressing this intermittent shortage is a top priority,” Health Canada said. “Together with our partners, Health Canada is looking at ways to conserve existing supply, expedite resupplies to pharmacies and access foreign-authorized supply or alternatives, where possible, during this temporary shortage.”
It’s clear that accessing Ozempic, or rather, semaglutide, isn’t easy. It also comes with a hefty price tag, about $200 to $300 a month, because Ozempic isn’t typically covered for weight loss under insurance plans, doctors told Global News.
Amid these shortages and high prices, some have turned to a particular natural remedy to shed pounds: berberine.
What is berberine?
Searching through videos tagged #berberine on TikTok produces a slew of glowing recommendations about the supplement. Users providing weekly updates about their weight loss journey gush about its effectiveness.
But experts told Global News that proof berberine is effective for weight loss is dubious — and calling it Nature’s Ozempic is tantamount to “fake news,” according to Dr. Sean Wharton, an internal medicine physician and weight management specialist.
Many of the claims made about berberine haven’t been backed up by peer-reviewed research, Dr. Wharton told Global News.
Most of the studies on the supplement, which is derived naturally from plants of the genus Berberis, were conducted on mice or have sample sizes lower than 100 people.
A 2022 meta-analysis of 49 studies found that berberine can improve insulin resistance and have metabolic benefits, and has a small, but statistically significant, benefit for weight loss.
But just because it’s a “scam,” Dr. Wharton says, and likely won’t give you the weight-loss benefits you’re looking for, doesn’t mean it’s dangerous to take.
Berberine has been used for thousands of years in Chinese traditional medicine to treat diarrhea and other gastrointestinal issues. The oldest-known evidence of berberine being used as a remedy dates back to 650 B.C. A clay tablet in the library of an Assyrian emperor states that the barberry fruit (Berberis vulgaris) was used as a blood-purifying agent.
Taking berberine consistently, and in a concentrated form, however, may cause stomach upset and other issues, Dr. Wharton warns. This could unfold if vitamin companies look to cash in on the recent craze, cut corners, and don’t formulate their supplements properly.
In the U.S., companies selling berberine alongside health claims on their websites have been sent notices of violation by the Food and Drug Administration.
In Canada, Dr. Wharton thinks the government should be proactive about countering unfounded health claims that pick up steam online.
“There should be some responsibility at the government level, when this type of thing happens, to legislate or to educate or to get something out there, so that the regular population isn’t duped,” Dr. Wharton says.
People who talk about taking berberine online often note how all other methods of weight loss have failed them. No amount of dieting and exercising worked.
While obesity has been framed as a lifestyle choice or a consequence of a lack of willpower, doctors are increasingly understanding the disease as a chronic, life-long condition potentially influenced by hormones, physiology, mental health and environmental factors like racism and poverty.
According to the Yale School of Medicine, drivers of obesity like processed foods, stress, and lack of sleep can pathologically alter the system of hormones that the body uses to regulate itself, making it “extremely difficult to lose weight.”
Ozempic, and other obesity drugs, target those hormones. And in treating obesity medically, and not as an issue of willpower, these drugs have seen great success in causing weight loss. Diet and exercise are still the cornerstone of weight management, experts say, but in conjunction with these lifestyle changes, patients can see incredible results with obesity medications.
While most of these obesity drugs are administered as once-weekly injections, one experimental drug is pill-based, and has the potential to skirt around the supply issues that have plagued injectable weight loss drugs.
Having more options for treatment is one benefit, but having new drugs enter the market could also potentially drive prices down across the board and make obesity treatment more accessible, Dr. Wharton hopes.
Mounjaro and retatrutide
Though you may not have heard of them yet, Mounjaro and retatrutide are two obesity drugs currently outpacing Ozempic in terms of weight loss results in clinical trials.
A study in the New England Journal of Medicine, which Wharton co-authored, found that on average, patients lost 15 per cent of their weight after taking Ozempic for 68 weeks (a year and four months).
A study on Mounjaro, a drug that was approved for use in Canada just last year, found that patients, on average, saw 16 per cent weight loss after taking it for 72 weeks (a year and five months).
Retatrutide is still an experimental drug, and hasn’t been around long enough to get comparable data to Ozempic and Mounjaro, but a phase 2 trial found that patients taking retatrutide lost 24 per cent of their body weight in just 11 months.
Mounjaro and retatrutide both work in a similar way to Ozempic, but are able to go another step further when it comes to weight loss. To understand why, we first have to understand how Ozempic treats type 2 diabetes and obesity.
Ozempic is just a brand name; what we’re really talking about is semaglutide. This molecule mimics a hormone that we naturally produce in our bodies called glucagon-like peptide 1, GLP-1 for short.
GLP-1 is created in the pancreas and signals the body to increase insulin production. It also blocks the release of another hormone called glucagon (the G in GLP-1), which tells the liver to release more glucose (sugar) into the bloodstream. In summary, semaglutide mimics this GLP-1 hormone and can trick the body’s intricate system of chemical receptors to boost insulin and lower blood sugar.
It’s clear to see why semaglutide works as a diabetes treatment, but researchers are less sure how it works for weight loss. It appears that GLP-1 slows the movement of food through the stomach, a process called gastric emptying.
Because of this, people who take semaglutide may feel fuller faster, and for longer periods of time. A woman who has been on semaglutide for four years told Global News that she would feel full after eating two pieces of cauliflower.
There is some evidence that semaglutide works on the brain to stop food cravings, with some scientists noting an increase in anecdotal reports of semaglutide helping curb addictive behaviours like smoking and drinking.
Mounjaro builds on the same mechanism Ozempic uses to spark weight loss. While Ozempic mimics one hunger-regulating hormone, GLP-1, Mounjaro mimics two hormones, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide).
Retatrutide ups the ante by mimicking three hormones: GLP-1, GIP and glucagon.
According to Dr. Wharton, the GLP-1 hormone probably confers the most weight-loss benefit. But having all three hormones is like “having a running back, trying to get into the end zone with two blockers.”
“The running back by himself probably does pretty good — and we’re seeing that the semaglutide molecule is amazing — but with two blockers he’s probably going to do really well,” Dr. Wharton says. “And that’s why retatrutide seems to be working so much better.”
Dr. Wharton says the arrival of these new drugs is great for doctors and patients alike, because it means that there are more options for care and more competition in the market could drive these drug prices down across the board.
But because they are so similar to Ozempic, these alternatives are susceptible to the same supply problems that have plagued the in-demand drug.
While there is no Mounjaro shortage in Canada, the drug has been in short supply in the U.S. since late last year, according to the FDA.
Orforglipron
“These large molecule injectable products are sensational,” Dr. Wharton says, describing drugs like Ozempic and Mounaro. “But they’re hard to make, hard to store and hard to ship.”
Drugs like this have to be refrigerated, which complicates the logistics of making and distributing them. And we’ve seen with shortages in the U.S. that demand for these drugs is outpacing supply.
“So what are you going to do? Well, there are small molecules that are now activating the GLP-1 receptor, giving you the same impact on blood sugar and weight change, which is going to change the entire field,” Dr. Wharton says.
“It’s like Henry Ford telling you we can make 100 cars in the time it takes to make one.”
The experimental medication that Dr. Wharton is talking about is called orforglipron, which can be administered as a pill instead of an injection, and he was involved in a study measuring its effectiveness.
After 36 weeks, or about nine months, patients enrolled in the study saw weight loss of up to 15 per cent, meaning orforglipron seems to be performing on-par with injectable obesity drugs.
“I do think that this has the potential to solve the supply problem,” plaguing injectable drugs, Dr. Wharton says.
He notes these pills can be made more easily and at lower cost to drug companies, they don’t require refrigeration and they’re easier for patients to take. Cheaper options for treatment is important because people affected by type 2 diabetes and obesity can face barriers to accessing medication, Dr. Wharton says.
Not everyone can afford to shell out $200 to $300 for Ozempic, but if this new pill can keep costs lower, it could go a long way in democratizing obesity care.
Concerns about obesity drugs
With clinical trials showing rapid weight loss among patients who take obesity drugs, some have been left wondering if shedding pounds so fast is safe.
Disability rights scholar and assistant professor Fady Shanouda of Carleton University is concerned about the fact that people who stop taking Ozempic often regain the weight they lost. This process is called weight cycling, and can be more detrimental to the body than simply staying at a stable, higher weight.
“When you take Ozempic and lose a bunch of weight, often very quickly, and then you regain that weight even at a faster rate — there are more health consequences associated with that,” Shanouda said.
He believes that drugs like Ozempic can have a “coercive” effect on people in larger bodies because of societal expectations to be thin. Instead of accepting their bodies, people may feel pressured to lose weight in a way that actually makes them less healthy.
“I’m not invested in people feeling bad about their bodies,” he said. “Unhealthy bodies should still be allowed to exist in our world.”
Shanouda says he would never tell someone to stop taking Ozempic, but he wants people to be aware that the drug can come with serious side effects like vomiting, nausea and even stomach paralysis.
“I know many people who are on Ozempic for diabetes and hate it because they can’t eat anything because their appetites are so suppressed,” he said. “I see a lot of people sort of withering away, especially older folks.”
Shanouda’s observations align with the experiences of Susanne Brown, a woman who has been on Ozempic for four years.
For Brown, Ozempic has been life-changing and has allowed her to hit her fitness goals. But she also likened being on Ozempic to “doctor-approved anorexia,” and said she felt addicted to losing weight on the drug.
Because her appetite was so suppressed on Ozempic, she fell into dangerous eating habits.
Brown recalls that she had to take caffeine supplements to stay awake during the day and to have enough energy to work out because she wasn’t getting enough nutrition on Ozempic. Eventually, she became anemic and her hair started to fall out.
Even with these distressing downsides, Brown said she would never discourage someone with obesity from taking Ozempic, in part because of how much better society treats her now that she’s physically smaller. Brown’s experiences bring into focus the weight bias that many people experience when they live in larger bodies, and how Ozempic can feel like a godsend. But in the wrong context, Ozempic can do more harm than good.
That’s why weight specialists say that Ozempic should only be prescribed to obese people when their weight causes other health problems or stops them from enjoying life.
“If you’re a larger body size and perfectly healthy, then you should be called ‘beautiful,’” he says.
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This article is not medical advice. Please consult a medical professional before deciding to take any medication.
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