Drugs like Ozempic and Wegovy, which are called GLP-1 agonists, have more benefits than risks when taken for approved use, according to a comprehensive analysis of their effects on 175 conditions. The same may not be true for people taking the drugs for other purposes.

“In this new land of GLP-1, we really wanted to map out the benefits and risks for all the conditions that could possibly be 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, 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 abuse 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, which means we can examine less frequent effects, says Al-Aly.

To get 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 received only standard care during the same period, and assessed the risks of both groups developing 175 different health conditions.

The team found that those taking GLP-1 agonists had a lower risk of 42 conditions. For example, their risk of heart attack decreased by 9 percent and their risk of dementia decreased by 8 percent. The odds of this group developing suicidal thoughts or substance use disorders, including dependence on alcohol and opioids, also dropped by about a tenth—even when the team took into account factors that could influence the results, such as participants’ age, gender, and income levels.

However, there were downsides for those taking GLP-1 drugs. They were more likely to experience 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 an inflamed pancreas or drug-induced pancreatitis. Overall, 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 effect on risk levels.

The fact that these drugs affect such a wide range of conditions is still surprising, although exactly why they have this effect is unclear. “They reduce obesity, which is kind of the mother of all diseases—you treat it, and then you get benefits in the heart, the kidney, the brain, and everywhere else,” says Al-Aly. They also dampen general organ-damaging inflammation and appear to target parts of the brain related to addiction, he says.

One problem with the analysis is that the team did not report the actual number of people affected by each condition, making it difficult 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 attack and dementia are probably worth taking seriously, he says, the links to rare conditions like pancreatitis may involve a very small number 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 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 company.

But for those without these conditions, such as non-obese people buying the drugs to lose weight, the picture may differ. “We have no idea if the benefits will outweigh the risks,” says Drucker.