GLP Receptor Agonists and Opioid Craving: What a Small, Messy Pilot Trial Actually Showed

The same class of drugs behind Ozempic and Wegovy is now being tested for something that has nothing to do with metabolism: whether it can reduce craving in people being treated for opioid use disorder. The early data is genuinely interesting. It’s also small, incomplete, and worth reading carefully rather than headline-first.

Why anyone thought to test this at all

GLP receptor agonists don’t only act on the gut and pancreas. The same receptor shows up in brain regions involved in reward and motivation, and animal studies have shown that activating it reduces self-administration and drug-seeking behavior for a surprisingly wide range of substances, not just food. In rats, GLP receptor agonists have been shown to reduce responding for alcohol, nicotine, and cocaine, and more recent work extended that same pattern to heroin specifically, reducing heroin taking, heroin seeking, and reinstatement of drug-seeking after a period of abstinence. That consistency across four separate substance classes is what moved this from an interesting animal finding into an actual human pilot trial.

The trial and what it found

A team at Penn State, led by Patricia Grigson and Scott Bunce, ran the first randomized, placebo-controlled trial testing a GLP receptor agonist specifically for opioid craving. Patients in residential treatment for opioid use disorder at the Caron Treatment Center were randomized to receive either liraglutide or placebo over a three-week protocol, with craving measured multiple times a day through ecological momentary assessment rather than a single end-of-study questionnaire.

The topline result, presented at the American Association for the Advancement of Science annual meeting in February 2024: patients on liraglutide reported a 40% reduction in opioid craving compared to placebo, and the effect showed up even at the lowest dose tested. Among patients already taking buprenorphine, the standard medication for opioid use disorder, adding liraglutide increased the likelihood of reporting zero cravings at all, an effect that became statistically meaningful roughly ten days into treatment as doses were titrated upward.

The part that gets left out of the headline

Twenty patients were randomized into this trial. Only nine of them completed it. Gastrointestinal side effects, nausea in particular, the same class of side effect that shows up across essentially every GLP drug, drove most of the dropouts, especially at higher doses. Patients who were also taking buprenorphine alongside liraglutide tolerated it better and dropped out less often than those on liraglutide alone, which is itself a useful finding, but it doesn’t change the fact that more than half the randomized sample didn’t make it to the end.

This is also, as of this writing, conference-presented preliminary data rather than a completed peer-reviewed publication. The full manuscript is described as being in preparation in later citing papers. That doesn’t make the finding meaningless, a 40% reduction in a randomized, placebo-controlled design is a real signal, but it does mean the result hasn’t yet gone through peer review, and a trial this small, with a completion rate this low, isn’t built to settle anything on its own.

What happens next

Researchers didn’t stop at the pilot. A much larger follow-up is now underway: a 200-participant, randomized, double-blind, placebo-controlled trial testing semaglutide specifically in outpatients enrolled in standard opioid use disorder treatment programs, split evenly between people on buprenorphine and people on methadone. That trial is designed to answer the question the small residential pilot couldn’t: whether this effect holds up in a real-world outpatient population, at a scale large enough to draw a real conclusion from.

Until that data reports, the honest summary is this: a small, imperfect trial found a real and interesting signal, and a much bigger, better-designed trial is already running to find out if it’s a durable one.

References

Grigson, Patricia S., and Scott Bunce. “Use of a GLP-1 Agonist to Treat Opioid Use Disorder in Rats and Man.” Clinical trial protocol, NCT04199728, Penn State College of Medicine.

Various authors. “Ecological Momentary Assessment and Cue-Elicited Drug Craving as Primary Endpoints: Study Protocol…” Addiction Science & Clinical Practice, 2024.

Various authors. “Efficacy of the GLP-1 Receptor Agonist, Semaglutide, in Abstinence from Illicit and Nonprescribed Opioids…” Addiction Science & Clinical Practice, 2025.

STAT News. “Opioid Cravings Were Reduced by Anti-Obesity Drug in Small Study.” February 2024.