Semaglutide may reduce opioid overdoses, a new study suggests 

A wildly popular diabetes and weight-loss drug may also protect people from overdosing on opioids.

That’s the implication of a new study that examined health records of people with type 2 diabetes and opioid use disorder. People prescribed semaglutide, which is sold under the brand names Ozempic and Wegovy, were roughly one-third to one-half as likely to overdose on opioids during a one-year follow-up as people prescribed a different diabetes drug. 

“It’s a big decrease,” says Rong Xu, an AI and biomedical researcher at Case Western Reserve University in Cleveland whose team reports the findings September 25 in JAMA Network Open.

More than 80,000 people in the United States died of opioid overdoses in 2023, so a new preventive strategy could save lives. But Xu is careful to point out that the study does not prove that the medication curbs opioid overdoses. “We can only say semaglutide is associated with reduced risk,” she says. 

The findings set the stage for clinical trials that directly test semaglutide’s effects, Xu adds.

The new work is the first to suggest that this type of drug could have such a protective effect in people, says behavioral neuroscientist Patricia “Sue” Grigson of Penn State College of Medicine in Hershey. “And that is a pretty remarkable finding.”

Semaglutide belongs to a family of drugs that mimic the gut hormone GLP-1 (SN: 8/29/23). Originally approved for diabetes, semaglutide and its relatives have gained fame — and notoriety — in recent years as weight-loss medications (SN: 12/13/23). But evidence is stacking up that the drugs may do more than help people with diabetes and obesity — they appear to be a kind of medicinal Swiss Army knife. 

Studies in rats and mice have hinted that semaglutide can curb addictive behaviors (SN: 8/30/23). Early results from Grigson’s team suggest that a related drug, liraglutide, reduces opioid cravings in people with opioid use disorder (SN: 2/17/24). And a handful of studies from Xu’s team this year suggest that semaglutide may offer some benefits to people addicted to alcohol, tobacco and cannabis.

For the latest study, Xu’s team analyzed electronic health records of more than 33,000 people prescribed semaglutide or a handful of other diabetes medications and counted opioid overdoses over the next year. Though overall numbers were low, people prescribed semaglutide were less likely to overdose than people prescribed other medications. The researchers logged 35 overdoses across 2,605 people on semaglutide, for example, compared with 76 out of 2,605 people on metformin. 

Scientists don’t know why semaglutide may have this protective effect. It’s possible people on the medication crave opioids less, and simply don’t use as much of the drugs. That would make them less likely to overdose, Grigson says. 

In November, Grigson’s team will begin enrolling people with opioid use disorder in a new clinical trial. Participants will take semaglutide along with one of two standard treatments for the disorder, and researchers will track how the drug combos affect their ability to abstain from opioids. 

And Xu’s team has now set its sights on stimulants: Perhaps semaglutide could help people who use methamphetamines and cocaine. She thinks the medication may tinker with some underlying biological mechanism that drives drug cravings in general. 

Pharmacoepidemiologist Serena Jingchuan Guo wonders if the drug could one day be used before addiction sets in, for instance as part of a pain management plan for patients prescribed opioids for pain relief after surgery. Perhaps taking semaglutide at the same time could prevent people from getting hooked on opioids in the first place, suggests Guo, of the University of Florida in Gainesville. 

But she cautions that many questions about semaglutide and its relatives remain, like what molecular buttons the drugs are pushing in the body to trigger its varied effects. People think of it as a “miracle drug,” she says, but “there are so many unknowns.”