It’s the drug that made Hollywood skinny. Rebel Wilson and Elon Musk both admit owing their slimmed-down silhouettes to it. But there’s much more to Ozempic than weight loss. This week, a trial found that semaglutide – the active ingredient in Ozempic and Wegovy – cut the risk of heart attacks and strokes in overweight people by a fifth. It was equally effective in people who didn’t lose any weight at all.
Semaglutide was first developed to treat type 2 diabetes. Much has been written about the drug’s immediate side-effects, which vary from nausea (Stephen Fry has said he had to give up Ozempic because of how sick it made him), constipation and sagging skin on the face.
But it is now being studied for other side effects beyond weight loss, and as a potential treatment for many other conditions, with promising results. John Deanfield, professor of cardiology at University College London, says that semaglutide and drugs like it could “transform many chronic diseases of ageing”.
So, what are some of the other surprising benefits of the blockbuster obesity drug?
How it could help to treat Parkinson’s disease
A diabetes drug very similar to semaglutide can slow the development of the symptoms of Parkinson’s disease, according to the results of a recent clinical trial. Parkinson’s damages the brain and causes progressively severe problems with movement.
But people who took the drug, called lixisenatide, for a year showed no worsening of their symptoms, a marked improvement over people taking a placebo. Like semaglutide, lixisenatide mimics the action of a gut hormone called GLP-1, which promotes a sensation of fullness.
Several studies have suggested that semaglutide also lowers inflammation, the mild rise in specific immune system activity that’s been linked with many diseases. Studies show that semaglutide can lowers the level of a compound in the blood called C-reactive protein, a known marker of inflammation, by up to 49 per cent.
“We think this anti-inflammatory effect may protect nerves in the brain,” says Alex Miras, a clinical professor of medicine at Ulster University, describing the discovery as “truly exciting”.
Trial to test protection against severity of Alzheimer’s
Novo Nordisk, the pharma giant behind semaglutide, is behind a major trial of the drug in people with early Alzheimer’s. The aim is to see if it can arrest the disease before it becomes severe. The study began in 2021 and is expected to report this year.
The company says: “Evidence suggests that over time, chronic inflammation in the brain could result in the inability of neurons to communicate and eventually die.” Reduced blood supply to the brain may also starve it of nutrients. The hope is that semaglutide will reverse both these issues.
Professor Miras says, “Studies show that GLP-1 drugs can protect nerves in the brain. I think we will see the same kind of results for Alzheimer’s as we’ve seen in Parkinson’s, and some people are even speculating about multiple sclerosis.”
Cure cravings
Some people taking drugs such as Wegovy and Ozempic have reported surprising — and highly desirable — side effects: Their desire for alcohol evaporates. Their need for nicotine goes up in smoke. They even crave recreational drugs less. Both actor Stephen Fry and presenter Jeremy Clarkson have noted the effect. Fry said, “‘The first week or so, I was thinking, “This is astonishing. Not only do I not want to eat. I don’t want any alcohol of any kind. This is going to be brilliant.” Clarkson said, “I can open the fridge, where there’s half a chicken and a juicy bottle of rosé, and I want neither.” These anecdotal reports suggest the possibility that semaglutide and similar drugs may be repurposed as treatments for addiction. Last year, a study showed that rodents who were tricked into becoming alcohol-dependent drank less when dosed up with semaglutide. In 2022, another study found that liraglutide, a close relative of semaglutide, reduced heroin seeking in rats. Multiple trials are now underway in humans, looking at whether semaglutide can tame the desire for drugs, smoking and drinking. Nicola Jones*, 54, says her drinking ramped up because of stress and menopausal symptoms. But since starting on Wegovy two months ago, “I have totally and utterly lost any appetite for alcohol.” Prof Miras says, “It seems that in some people, the drugs reduce reward cues in the brain, so there could well be a reduction in their addictions”.
Potential for reduction in the risk of some types of cancer
In early animal studies, semaglutide seemed to raise the risk of thyroid cancer, which led to scary warnings on packaging and a natural fearfulness in people otherwise tempted by the medication. Some early studies also suggested the drug could increase the risk of pancreatic cancer in mice and, therefore, people. However, new research has mostly dismissed these worries.
Professor Le Roux says that mice have very different pancreases to humans. “It was a species-specific problem.” And Prof Miras says: “There is no evidence that they cause any type of cancer.” Even better, some studies suggest semaglutide could be preventative.
Partly, this is because of weight loss. Recent research from the University of Malmo in Sweden has found that almost half of cancer diagnoses are linked to obesity, with excess weight fuelling around 30 different types of the disease.
A 2023 study in JAMA Oncology found that GLP-1 drugs cut the risk of colorectal cancer by 44 per cent in people with type 2 diabetes. One small study has found that semaglutide helps increase the function of so-called NK, or natural killer cells, which destroy cancer cells before they can grow into tumours, which could mean that it works across multiple types of the disease.
Reduce the risk of heart attack and stroke
The most extensive study yet on semaglutide has revealed that it can cut the risk of heart attacks or death in pre-existing heart patients by 20 per cent. Of the 8,803 patients on the placebo jab, 701 (or 8 per cent) suffered a heart attack. But in the semaglutide group it was only 569 (or 6.5 per cent).
Crucially, the same reduction happened even in people who did not lose weight. Prof Deanfield, speaking at the 2024 European Congress on Obesity in Venice, said that the drug was a ‘game-changer’ that should change how the NHS treats the eight million people in Britain with heart disease.
Professor Miras was a principal investigator at the trial. He says, “We thought semaglutide would improve cardiovascular health by causing weight loss. But that wasn’t the mechanism.”
So how does it work? “We think semaglutide’s anti-inflammatory effect protects the arteries.” He also says that semaglutide may have a “kind of anti-clotting effect”. Several studies have also found that the drug can improve the symptoms of heart failure, including improving people’s ability to walk. Studies also show that semaglutide can reduce blood pressure and improve cholesterol, benefiting heart health and reducing stroke risk.
Lowering the likelihood of anxiety and depression
There’s good news and bad news. While the drugs have been linked to suicidal thoughts in the past, it looks as if semaglutide is more likely to cheer us up. Prof Miras says, “There was an excellent report a couple of months ago showing the medication decreases suicidal ideation.”
In the study, researchers at the National Institutes of Health in the US found that people taking semaglutide had a lower incidence of suicidal thoughts compared to people taking other kinds of diabetes or weight loss medications.
A separate analysis of four million patient health records in the US showed that people taking a GLP-1 medicine for either diabetes or weight loss were less likely to experience anxiety and depression. However, Professor Miras admits “a small cohort of people may develop suicidal ideation. In this case, he says, “we cut down on the dose or stop the drug altogether”.