Weight-Loss Drugs Come With Serious GI Side Effects

There’s been a surge in demand for a class of diabetes drugs that are now popular for their serendipitous byproduct: weight loss.

The drugs belong to a class called GLP-1 agonists and include semaglutide, the main ingredient in Ozempic, Wegovy, and Rybelsus; tirzepatide, which is found in Mounjaro; and liraglutide, used in Victoza and Saxenda. While effective in helping people with diabetes to lose about 15% of their body weight, these drugs are also linked to some risk of gastrointestinal side effects, including inflammation in the pancreas and obstructions of the digestive system.

But how common are these risks in people who don’t have diabetes, and are increasingly taking the drugs to lose weight? On Sept. 28, the U.S. Food and Drug Administration (FDA) asked manufacturers of the semaglutide drugs to include a warning in the medication label about the possible risk of intestinal blockage, after receiving 8,500 reports of the condition from both diabetic and non-diabetic users.

Now, in a research letter published in JAMA, scientists at the University of British Columbia provide additional data on the magnitude of those risks for people taking them purely for weight loss. They report that among 4,700 people without diabetes taking some form of GLP-1 and 650 people taking an older, different combination of weight loss drugs, those taking GLP-1s had a nine times greater risk of pancreatitis and four times higher risk of both obstructed bowels and gastroparesis, which is a slower emptying of the stomach into the intestines.

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“We wanted to examine these risks taking diabetes out of the equation,” says Mohit Sodhi, a fourth year medical student at University of British Columbia and first author of the study, “since so many people are taking these [medications] specifically for weight loss and don’t have diabetes.”

While the researchers only studied semaglutide and liraglutide, they say the adverse effects in the GI system may occur with all drugs in the GLP-1 class, including tirzepatide, which the FDA has approved for treating diabetes but is still reviewing for weight loss.

The absolute risk of these side effects remains small, but given how many people are starting to take the medications not to treat diabetes but purely to lose a few pounds, these side effects could become significant. “Say that a million people are taking GLP-1s,” says Sodhi. “If you look at the incidence of gastroparesis in our study, it was about 1%. If you take 1% of 1 million, that’s 10,000 people who are potentially experiencing that adverse event. Blow that up to millions more patients taking these drugs, and the numbers can get extremely high.”

For people with diabetes, who are more vulnerable to other health complications related to uncontrolled blood sugar, such as circulation issues and kidney and eye abnormalities, the benefits in controlling those conditions may outweigh the gastrointestinal risks. But for those without diabetes, those risks may outweigh the benefits of losing a few pounds. While there are some studies showing other positive health outcomes associated with the weight loss drugs for people without diabetes, including reduction in heart disease risk, more research is needed to confirm those findings.

Additional studies are also needed to better understand why GLP-1 drugs have such adverse effects on the stomach and intestines. Some early work in both people with and without diabetes suggests that the medications slow the normal motion of the stomach and intestines, possibly even stunning the nervous system into inaction.

“We’re hoping that our paper will spur additional research to see if people can replicate our findings and hopefully give people more informed consent when using these medications,” says Sodhi.