Accumulating scientific evidence and industry interest from Eli Lilly, Altimmune and startup Baseline Therapeutics is driving further research on the therapeutic potential of GLP-1 receptor agonists in treating substance use disorders.
While alcohol use disorder affects nearly 30 million people in the U.S. alone, only three drugs are approved by the FDA to treat the condition, compared to dozens for diabetes and hundreds for cancer. Multiple companies are now looking to end that drought, testing out the potential of GLP-1 receptor agonists in various substance use disorders.
These drugs could become “a new blockbuster class” for this group of conditions, predicts Nicholas Reville, head of strategy at Baseline Therapeutics.
Baseline launched in January to test a GLP-1 compound in alcohol use disorder (AUD) with an eye toward future indications. Elsewhere, obesity heavyweight Eli Lilly and liver disease–focused Altimmune are running mid- or late-stage trials in AUD and opioid use disorder. Those studies are expected to complete in the next two years. And the sector has considerable revenue potential, with the global substance abuse therapeutic market expected to hit $12.4 billion by 2033.
Adding to the momentum is a steadily accumulating body of evidence suggesting GLP-1s have a positive effect in these indications. Just this month, a sizable study of U.S. veterans published in The BMJ made international headlines for finding an association between GLP-1s and a reduced risk of substance abuse and related severe outcomes.
While it’s an exciting time for the field, more—and larger—clinical studies are needed to determine whether these drugs really work as treatments for addiction, Lorenzo Leggio, an addiction researcher and physician-scientist at the National Institutes of Health, told BioSpace. “This is the part that we’re still missing.”
Eli Lilly, Baseline All In on Substance Use Disorders
Researchers are on the case. More than a dozen clinical studies are looking into GLP-1s for alcohol-related disorders alone. A handful of trials registered on ClinicalTrials.gov—mostly Phase 2 studies run by academic institutions investigating semiglutide’s effects on alcohol intake—are slated to release results within weeks or months.
As for larger industry-run efforts, Lilly leads the pack with ongoing studies evaluating its compound brenipatide, which targets both the GLP-1 and GIP receptors, in two Phase 3 trials for AUD and a Phase 2 study for relapse in tobacco use disorder. A separate Phase 2 study will test the drug in conjunction with other medicines in people with opioid use disorder. Those trials are expected to be completed in 2027 and 2028, a company spokesperson confirmed.
Novo Nordisk, Lilly’s prime competitor in the GLP-1 space, has been quieter regarding its own addiction focus. A Phase 2 trial investigating semaglutide’s effects on liver damage and alcohol use wrapped earlier this year, with results still to be released.
Semaglutide has previously demonstrated potential in AUD. A small U.S.-based academic study published in JAMA Psychiatry in February 2025 showed that Novo’s semaglutide—marketed as Ozempic for type 2 diabetes and Wegovy for obesity—reduced alcohol intake and alcohol cravings after nine weeks of treatment. While semaglutide did not decrease the number of drinking days, the number of drinks consumed per drinking day went down.
As of March 2025, however, Novo—which has been battered by disappointing trial results, sliding sales guidance and layoffs during the past year—had no plans to study the drug in other conditions, a company spokesperson told BioSpace at the time. The Danish pharma did not respond to questions about future research for this article.
As Baseline’s entry into the space demonstrates, it isn’t just a big players’ game. The startup aims to initiate two Phase 3 trials of its compound BT-001 later this year, CEO Morris Birnbaum told BioSpace. The trials will test two different doses of the drug in patients with AUD. Once those studies are initiated, Baseline will seek additional funds for further studies—most likely in stimulant use disorder, Birnbaum said.
Meanwhile, Maryland-based Altimmune is testing a different approach with pemvidutide, which targets both the GLP-1 and glucagon receptors. While the company’s flagship target is metabolic dysfunction-associated steatohepatitis (MASH), Altimmune completed enrollment last November for a Phase 2 trial to determine whether the compound reduces drinking in people with AUD and overweight or obesity. Study completion is expected in June.
Pemvidutide’s dual action gives it the potential to target both alcohol dependence and early liver damage, and tolerability data have so far been particularly compelling, Chief Medical Officer Christophe Arbet-Engels told BioSpace.
Baseline’s Birnbaum said having trials run by multiple different entities is important, adding that there will likely be some segmentation as different drugs and companies focus on particular indications and patient groups.
“This is a very large population of patients,” he told BioSpace. “There’s plenty of opportunity for multiple players in this market.”
Evidence Mounts
These current and upcoming trials stand to provide much-needed scientific support for the use of GLP-1s in substance use disorders. Until now, enthusiasm has largely been driven by years of animal studies, anecdotal data and epidemiological research suggesting the drugs suppress cravings and reduce substance abuse-related behaviors.
In the recent BMJ study, for example, researchers analyzed the health records of more than 600,000 U.S. veterans with diabetes and found that, compared to people taking other medications, diabetics on GLP-1s had a 14% reduction in the risk of developing a substance use disorder. Among those who already had a disorder, there was a 26% reduction in hospitalizations related to that condition.
The findings dovetail with earlier observational research among people using opioids and alcohol—but by their nature, these studies cannot definitively determine whether GLP-1s caused the improvements.
Previous clinical trials designed to nail down a causal relationship have been mixed. One early randomized, placebo-controlled trial of exenatide, an older GLP-1 drug developed by Lilly and Amylin Pharmaceuticals, failed to show a reduction in alcohol consumption in people with AUD after 26 weeks of treatment—though a subgroup analysis did find a reduction in alcohol intake among patients with AUD and obesity.
Another trial in Switzerland that tested Lilly’s Trulicity in people trying to quit smoking found no effect on this outcome, despite an earlier pilot study of exenatide in the U.S. showing an apparent benefit. A secondary analysis identified a reduction in alcohol consumption among people who completed a full course of treatment.
Baseline’s Reville emphasized that not all GLP-1s are created equal, and that newer drugs—including Novo’s semaglutide and Lilly’s tirzepatide (marketed as Mounjaro and Zepbound)—likely hold more promise than their predecessors.
He and others who spoke to BioSpace pointed to the success of last year’s JAMA Psychiatry study as an early potential sign of this. “You’re going to start seeing a lot more data coming really soon on the current generation,” Reville added.
Still To Learn
In addition to key efficacy data on those newer drugs, researchers said they hope ongoing trials will provide more information about which patients will most benefit from GLP-1s.
“Even a drug with potentially large effects on substance use will not be effective for everyone,” Joseph Schacht, associate professor of Psychiatry-Substance Abuse at the University of Colorado and an investigator on Altimmune’s AUD trial, told BioSpace in an email.
With such a high-risk group of patients, the safety of GLP-1s must also be a major consideration for research, Leggio said—though he noted that, encouragingly, clinical studies don’t seem to be turning up concerning side-effects in these patients so far.
While cautioning that it’s still too early to say whether GLP-1 will be successful for these disorders, he added that he is “very optimistic.”
And regardless of that success, the intensified investment in and research on these disorders is a boost for these historically neglected conditions, Leggio added. “It’s wonderful for the field, and it’s wonderful for our patients.”
