Anti-obesity drug reduces opioid craving in small study

DENVER — The GLP-1 drug liraglutide significantly reduced opioid craving in a small analysis published Saturday. This is the first randomized controlled trial testing an anti-obesity drug for opioid addiction. kill those around you 80,000 people every year in America.

Among 20 patients with opioid use disorder, those receiving liraglutide had a 30% reduction in opioid craving over a three-week study, according to data presented here at the American Association for the Advancement of Medicine. This was evident even at the lowest dose of liraglutide. Scientific conference.

Among patients already taking buprenorphine, which is approved by the FDA to treat opioid use disorder, those also taking liraglutide were more likely to report having zero appetite than those in the placebo group. . This effect became statistically significant after day 10 of the study, as patients gradually increased their liraglutide dose. Andrew Saxon, an addiction psychiatrist at the University of Washington who was not involved in the study, said that because liraglutide and buprenorphine may target different mechanisms, “the additive effects of these two drugs are That suggests something.”

In most cases, there were no significant differences in side effects between patients who received liraglutide and those who received a placebo, suggesting that this GLP-1 drug is safe in patients with opioid use disorder. However, gastrointestinal disorders were twice as common in the liraglutide group, and only nine patients completed the three-week trial, a major cause of the study's high dropout rate.

However, Scott Vance, a clinical psychologist at Penn State University and one of the trial's principal investigators, found that patients who received both liraglutide and buprenorphine experienced more gastrointestinal distress than participants who received liraglutide alone. and low dropout rates, suggesting that a combination approach may reduce symptoms. Some of these issues. Additionally, the finding that appetite was significantly reduced at the lowest dose of liraglutide suggests that many of these side effects can be alleviated by maintaining low doses, although this requires further research.

The study was conducted at the Caron Treatment Center in Warnersville, Pennsylvania, and was funded by the donor family, the National Institute on Drug Abuse, and Novo Nordisk, the pharmaceutical company that sells liraglutide as Victoza for diabetes and Saxenda for obesity. It was carried out in response to the All patients were residents and had recently undergone medication-assisted withdrawal.

Approximately 80% of the participants were white men, and all received notifications on their cell phones four times a day to assess their self-reported cravings. “This allowed us to ask people how much they were craving right now, rather than just yesterday or last week,” said Dr. Petersen, director of the Pennsylvania Translational Addiction Center and another principal investigator on the trial. said one Patricia Grigson.

The clinical trial is the culmination of seven years of animal research conducted in Grigson's lab and shows that GLP-1 targets three pathways leading to relapse. Environmental cues, stress, and the drug itself — as STAT does previously reported. The FDA has approved three of his drugs to treat opioid addiction, and recent research from the CDC and NIH estimates that: only 20% Percentage of patients receiving these treatments in 2021.

In addition to being consumed in lower doses, these drugs are also associated with: Significant recurrence rate (approximately 50%), please do not I also work In patients who have used fentanyl, buprenorphine and methadone may be stigmatized as opioid substitutes. Therefore, GLP-1 could be a promising alternative, or at least an adjunct to existing treatments, Grigson and Vance said.

However, due to the small sample size, limited diversity of participants, and relatively short trial, “we must be very cautious in interpreting these preliminary results,” said the researchers involved in the study. said Heath Schmidt, a neuropharmacologist at the University of Pennsylvania. A further limitation is that studies of patients in residential treatment facilities may not be representative. “It's very different than being at home or on the street, where you're surrounded by a lot of cues that promote relapse and craving,” Schmidt added. Additionally, those in treatment facilities are likely to be a subset of patients who are highly motivated and motivated to receive treatment.

However, perhaps the most significant limitation of these data is the high dropout rate, which not only limits the interpretation of the results but also highlights potential barriers to using GLP-1 in the treatment of drug addiction. Masu. “Nausea is one of the first withdrawal symptoms, and this patient population has extreme anxiety and fear of withdrawal,” Saxon said. “So they may interpret the nausea as, 'I'm in withdrawal and I need to get out of it as much as possible.'”

Despite these limitations, Christian Hendershot, a psychologist at the University of North Carolina at Chapel Hill who has studied GLP-1 in alcohol use disorder and was not involved in this study, says the data are proof of concept. and emphasized its importance as an experiment. A stepping stone to a greater challenge. “The reason these initial findings are great is because they actually investigated this question in a controlled environment,” Hendershot said. “We know that craving often predicts relapse. So, now that we've seen that reduction, the next question is whether a drug like liraglutide will suppress craving and relapse in its natural environment. is.”

Grigson and Bunce similarly emphasize the preliminary nature of the findings and the need for follow-up research. They are planning a randomized controlled trial of 200 people taking methadone or buprenorphine, half of whom will receive semaglutide and half who will receive a placebo, at three outpatient facilities in Pennsylvania, New York and Maryland. .

“alone dying every 5 minutes People are dying around the world from exposure to opioids, and we are alarmed,” Grigson said. “I feel very hopeful. There may be a new treatment for opioid use disorder.”

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