Semaglutide and other GLP-1 agonists are injected
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Drugs like Ozempic and Wegovy, which are called GLP-1 agonists, have more benefits than risks when taken for their approved uses, according to a comprehensive review of their effects in 175 conditions. However, the same may not be true for people who take drugs for other uses.
“In this new territory of GLP-1, we wanted to map the benefits and risks of all conditions that could plausibly be associated,” he says. Ziyad Al-Aly at Washington University in Saint Louis, Missouri.
The drugs are best known for helping to control type 2 diabetes and treat obesity. They mimic a hormone in the body, GLP-1, which lowers blood sugar levels and makes people feel fuller for longer.
Dozens of studies suggest that GLP-1 agonists may also reduce the risk of a host of other conditions, from heart disease to dementia to substance use disorders. These studies have involved hundreds or thousands of people and focused on one or a few conditions at a time, but millions of people are using the drugs, which means we can investigate less frequent effects, says Al-Aly.
To get a broader picture, he and his colleagues analyzed the health records of more than 200,000 people with diabetes who took GLP-1 agonists in addition to standard treatment over a four-year period. They also looked at 1.2 million people with diabetes who received only standard care at the same time, and both groups assessed their risk of developing 175 different health conditions.
The team found that those taking GLP-1 agonists had a lower risk of 42 conditions. For example, the risk of heart attack was reduced by 9% and the risk of dementia by 8%. The odds of suicidal thoughts or substance use disorders, including alcohol and opioid dependence, were reduced by a tenth in this group, even when the group took into account factors that may have influenced the results, such as such as the age, gender and income of the participants. .
There were downsides for people taking GLP-1 drugs, however. They experienced known side effects including nausea and vomiting, along with others not previously described. These include a 15 percent higher risk of kidney stones and more than twice the risk of inflammation of the pancreas or drug-induced pancreatitis. In all, risks were higher for 19 conditions, and for most conditions evaluated, including bronchitis, rheumatoid arthritis, and obsessive-compulsive disorder, taking GLP-1 drugs had no significant effect on risk levels.
The fact that these drugs affect a wide range of conditions is still surprising, although why they do so is not clear. “They’re reducing obesity, which is kind of the mother of all diseases; you treat that, and then you get benefits in the heart, the kidney, the brain, and everywhere else,” says Al-Aly. They generally slow inflammation that damages organs and appear to target parts of the brain linked to addiction, he says.
One problem with the study is that the team didn’t report the number of people affected by each condition, making the results difficult to interpret, he says. Daniel Drucker at the University of Toronto, where he has worked with obesity drug companies. While risk reductions in common conditions such as heart attacks and dementia are worth taking seriously, links to rarer conditions such as pancreatitis may involve very small numbers of cases and therefore pose little risk to most people. Al-Aly says the team will present specific case numbers in a future study.
Overall, the research confirms 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,” he says Stefan Trapp at University College London, who has also worked with an obesity drug company.
But for those who do not have these conditions, for example, those who buy weight loss drugs for non-obese people, the picture can be different. “We don’t know if the benefits will outweigh the risks,” says Drucker.
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