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 in 175 cases. However, the same may not be true for people who take medications for other uses.
“In this new territory for GLP-1, we wanted to map the benefits and risks of all the conditions that might plausibly be associated,” he says. Ziad Al-Ali At Washington University in St. Louis, Missouri.
These medications are 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 full longer.
Dozens of studies suggest that GLP-1 agonists may also reduce the risk of a wide range of other conditions, from heart disease to dementia and substance use disorders. These studies have included hundreds or thousands of people and focused on just one or a few cases at a time, but millions of people now use the drugs, which means we can check for less frequent effects, Al Ali says.
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 four years. They also looked at 1.2 million people with diabetes who received only standard care during the same period, and assessed both groups’ risks of developing 175 different health conditions.
The team found that those who took GLP-1 agonists had a 42 lower risk of developing the condition. For example, the risk of heart attacks was reduced by 9 percent, and the risk of dementia was reduced by 8 percent. This group’s odds of having suicidal thoughts or substance use disorders, including addiction to alcohol and opioids, also fell 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 people taking GLP-1 medications. They were more likely to suffer from known side effects including nausea and vomiting, along with others that had not been described before. These risks include a 15 percent higher risk of kidney stones, and more than twice the risk of pancreatitis, or drug-induced inflammation of the pancreas. Overall, risks were higher for 19 conditions, while for most of the conditions evaluated, including bronchitis, rheumatoid arthritis and obsessive-compulsive disorder, taking GLP-1 medications had no appreciable effect on risk levels.
The fact that these drugs affect a wide range of conditions is still surprising, although why this effect exists is unclear. “They reduce obesity, which is kind of the mother of all ills — you treat it and so you get benefits for the heart, kidneys, brain and everywhere else,” Al Ali says. They also generally reduce inflammation that damages organs, and appear to target parts of the brain associated with addiction, he says.
One problem with the analysis is that the team did not report the actual number of people affected by each case, making the results difficult to interpret, he says Daniel Drucker at the University of Toronto, who worked with obesity drug companies. While the reduced risk in common conditions like heart attacks and dementia is probably worth taking seriously, he says, the links with rare conditions like pancreatitis may involve a very small number of cases and therefore pose no significant risk to most people. Al Ali says the team will provide 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,” he says. Stefan Trapp at University College London, who also worked with an obesity drug company.
But for those who don’t have these conditions, such as non-obese people who buy weight-loss drugs, the picture may be different. “We have no idea whether the benefits will outweigh the risks,” Drucker says.
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