Semaglutide and other GLP-1 agonists are injected
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Drugs like Ozempic and Wegovy, called GLP-1 agonists, carry more benefits than risks when taken for their approved uses, according to a comprehensive analysis of their effects on 175 conditions. The same may not be true for people taking the drugs for other uses, however.
“In this new land of GLP-1, we wanted to really map the benefits and risks for all conditions that might be plausibly linked,” says Ziyad Al-Aly at Washington University in Saint Louis, Missouri.
The drugs are best known for helping people control type 2 diabetes and treat obesity. They mimic a hormone in the body, GLP-1, that lowers blood sugar levels and makes people feel fuller for longer.
Dozens of studies suggest GLP-1 agonists may also cut the risk of a slew of other conditions, from heart disease to dementia to substance use disorders. These studies have involved hundreds or thousands of people and focused on just one or a few conditions at a time, but millions of people are now using the drugs, meaning we can investigate less frequent effects, says Al-Aly.
To gain a more comprehensive picture, he and his colleagues examined the health records of more than 200,000 people with diabetes who took GLP-1 agonists in addition to their standard treatment over a four-year period. They also looked at 1.2 million people with diabetes who only received standard care across the same period, and assessed the risks of both groups developing 175 different health conditions.
The team found that those who took GLP-1 agonists had a lower risk of 42 conditions. For instance, their risk of heart attacks was reduced by 9 per cent and their risk of dementia dropped by 8 per cent. The odds of this group having suicidal thoughts or substance use disorders, including addiction to alcohol and opioids, also decreased by around a tenth – even when the team accounted for factors that could affect the results, such as participants’ age, sex and income levels.
There were downsides for the people taking GLP-1 drugs, however. They were more likely to experience known side effects including nausea and vomiting, along with others not described before. These include a 15 per cent higher risk of kidney stones and more than double the risk of an inflamed pancreas, or drug-induced pancreatitis. In total, risks were higher for 19 conditions, while for most of the conditions assessed, including bronchitis, rheumatoid arthritis and obsessive-compulsive disorder, taking GLP-1 drugs had no meaningful impact on risk levels.
The fact that these drugs do affect such a wide range of conditions is still surprising, although exactly why they have this impact is unclear. “They’re reducing obesity, which is sort of the mother of all ills – you treat it and subsequently get benefit in the heart, the kidney, the brain and everywhere else,” says Al-Aly. They also generally dampen organ-damaging inflammation and seem to target parts of the brain related to addiction, he says.
One issue with the analysis is that the team didn’t report the actual number of people affected by each condition, making it hard to interpret the results, says Daniel Drucker at the University of Toronto, who has worked with obesity-drug companies. While the risk reductions in common conditions like heart attacks and dementia are probably worth taking seriously, he says, the links to rarer conditions like pancreatitis might involve a very small number of cases and so pose little risk to most people. Al-Aly says the team will be presenting specific case numbers in a future study.
Overall, the research provides reassurance that the benefits of GLP-1 agonists outweigh the risks, at least for people with type 2 diabetes and obesity. “There are no red flags for this group,” says Stefan Trapp at University College London, who has also worked with an obesity-drug firm.
But for those without these conditions, such as people without obesity buying the drugs to lose weight, the picture may differ. “We have no idea if the benefits will outweigh the risks,” says Drucker.
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