Could popular weight loss drugs become the new treatment for addiction? Evidence is starting to mount
By Meg Tirrell, CNN
(CNN) — Evidence is mounting that the wildly popular weight-loss medicines known as GLP-1s may also hold potential for treating addiction, and the field may be on the verge of obtaining desperately needed answers through more study.
The drugs, approved to treat diabetes and obesity as Ozempic, Wegovy, Mounjaro and Zepbound, are used by millions of Americans. They help people lose weight by working in both the gut and the brain, acting on digestion, insulin and appetite, helping quiet cravings and what users describe as “food noise.”
So named for the GLP-1 hormone they mimic, the medicines have also shown success in cardiovascular disease, heart failure, sleep apnea and kidney disease. Addiction may be one of their next frontiers, an area where only small fractions of patients currently receive medications as treatment.
“If these drugs turn out to be safe and efficacious for treatment of substance-use disorder, because they are so broadly used for other reasons in our society, they would just automatically, de facto, become the most widely prescribed pharmacotherapy for addiction,” said Dr. W. Kyle Simmons, a professor of pharmacology and physiology at Oklahoma State University who studies GLP-1s in addiction. “We don’t have all the data yet, but it’s sure trending in the right direction, and that is a hopeful sign.”
Much of the research on the medicines in addiction so far has been in animals, work that’s helped elucidate how they might act on reward systems in the brain. There have also been a number of studies examining impacts on addiction in real-world use of the drugs prescribed for other diseases, as well as countless anecdotes of people’s personal experiences.
And although some smaller clinical trials have added to the drugs’ promise in areas such as alcohol-use disorder, larger ones are needed to confirm their effect, said Dr. Daniel Drucker, a pioneer of GLP-1 research at the University of Toronto.
Those answers may finally be close, after a slower start for interest and investment in trials of GLP-1 drugs in addiction. Now, Simmons said, “it’s exploding, frankly. There are a handful of well-designed, well-powered [trials] that are going to be reading out in the next six months, specifically with alcohol-use disorder and GLP-1.”
A glimpse into the VA
Until then, studies such as a newly published analysis of medical records continue to add to the hope.
Using databases from the US Department of Veterans Affairs, researchers at the Washington University School of Medicine in St. Louis analyzed substance-use disorder outcomes among more than 600,000 people with type 2 diabetes. They were treated with either GLP-1 medicines or those in another class called SGLT2 inhibitors.
The study found that people using GLP-1 drugs were less likely to develop an array of substance-use disorders or to have bad outcomes – such as hospitalization or drug overdose – if they’d already been diagnosed with one. The study was published Wednesday in the BMJ.
“We’re talking about a diabetes and obesity drug; we’re not talking about an addiction drug here,” said Dr. Ziyad Al-Aly, a clinical epidemiologist and chief of the Research and Development Service at the VA St. Louis Health Care System, who led the study. “What’s surprising is the breadth and consistency of effect across all of these different substances.”
Al-Aly and his team compared the risk that people would be diagnosed with substance-use disorders related to alcohol, cannabis, cocaine, nicotine, opioids and others. They found that GLP-1 use was associated with about 7 fewer people per 1,000 developing any substance-use disorder over the study period of three years.
“One of the most promising aspects of these findings is the evidence for potential protective effects across several types of [substance-use disorder] in the same dataset,” said Dr. Christian Hendershot, director of clinical research at the USC Institute for Addiction Science, who wasn’t involved in the new research but has run trials of GLP-1s in addiction. He pointed specifically to the study’s findings on cocaine and cannabis-use disorder, “for which we don’t have medications currently.”
An effect on drug overdose deaths?
The study also suggested that the medicines may help reduce risks for people who already have substance-use disorders. There, “the magnitude of risk reduction that we saw is quite profound,” Al-Aly said. “We saw a 50% reduction in drug-related deaths.”
Drug overdoses caused more than 79,000 deaths in the US in 2024, according to the US Centers for Disease Control and Prevention. But the death rate from drug overdoses has been declining, a trajectory researchers have attributed to changes in drug supply, greater accessibility of treatment and more widespread use of the opioid overdose reversal drug naloxone.
Given that millions of people are using GLP-1s, could they also be playing a role? Al-Aly said it’s possible, but it’s hard to say how probable.
“Whether it’s likely, and the magnitude or extent of its contribution to drug overdoses in the US, is really hard to extrapolate,” he said.
Dr. Caleb Alexander, a professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, suggested that the size of the effect on overdose deaths appeared “too large to be believable,” though he applauded a number of strengths of the new study.
“It’s a large and thoughtfully conducted observational study,” said Alexander, who wasn’t involved with the research. “The key concern is that people who start GLP-1 medications may differ in important ways from people starting other diabetes drugs.”
People who are starting GLP-1s could be more motivated to change their behaviors, be more engaged with their health care or receive more intensive follow-up from clinicians, Alexander said. “Those differences can influence outcomes like substance use.”
The study, having been done using medical records from the VA, is also “overwhelmingly male, and it is older than the general population,” noted Simmons, who also wasn’t involved in the research. “There’s always a concern about: Do these results generalize?”
More clinical trials needed
That’s why more randomized controlled trials are needed, Simmons emphasized. Those are studies that separate patients from the outset into different groups, ensuring that they’re well-matched, and then administer an intervention to one group to assess its safety and how well it works.
He is leading a trial evaluating use of semaglutide, the active ingredient in Ozempic, for alcohol reduction, and a similar trial is underway at the National Institute on Drug Abuse in Baltimore.
Trials are also now being planned or conducted on cocaine-use disorder and opioids. Novo Nordisk, the maker of Ozempic, said it would study its drugs’ effects on alcohol consumption in a trial of people with alcohol-related liver disease. And Eli Lilly, which makes the Ozempic competitor Mounjaro, is testing an experimental drug called brenipatide on alcohol, tobacco and opioid use disorders.
One concern about GLP-1 medicines had been whether they were associated with an increase in risk of suicide or suicidal thoughts, prompting European regulators to open an investigation into the issue in 2023. But subsequent studies, including a large review of US health records, found no such association, and this new study adds to those findings.
“We actually see a 25% reduction in suicidal ideation,” Al-Aly noted.
Still, he pointed out that a huge number of questions remain about how GLP-1s work and whether they should be prescribed for addiction: What happens if someone suddenly stops using them? Does the brain adjust to them over years of use, reducing their effectiveness? And could an impact on the reward circuitry in the brain have an effect on everyday enjoyment of life, desire and positive-risk-taking?
“I think we have to be cautious here,” Al-Aly said, adding to the calls for more research. “We don’t know what we don’t know about these drugs.”
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