Drugs originally developed to manage type 2 diabetes and obesity are attracting growing scientific interest for a very different purpose: treating substance use disorders. Researchers have found that GLP-1 receptor agonists are being investigated across a range of addiction conditions, but studies remain heavily concentrated in alcohol and tobacco use, leaving significant gaps for other substances.

The review, published in Addictive Behaviors Reports in January 2026, examined 192 records on ClinicalTrials.gov up to July 2025. Of those, 33 trials met the criteria for inclusion, covering conditions from alcohol use disorder (AUD) to cocaine and opioid dependence.

What the Trials Tell Us About GLP-1 Receptor Agonists

Alcohol use disorder dominated the landscape, accounting for 15 of the 33 qualifying trials. Nicotine and tobacco use disorder came second with nine trials, followed by cocaine use disorder (four), opioid use disorder (four), and methamphetamine use disorder (just one). Researchers found no clinical trials of GLP-1 receptor agonists for cannabis use disorder.

Semaglutide led the field as the most studied GLP-1RA, appearing in 15 trials. Exenatide followed with eight, and tirzepatide with six. Liraglutide, dulaglutide, and a newer agent called pemvidutide each appeared in one or two trials.

The findings underline just how early-stage this research area remains. Treatment durations ranged from as few as five days to 32 weeks. Researchers also measured outcomes in widely different ways, mixing self-reported data with objective measures such as urine toxicology results and breath alcohol concentration readings.

The Science Behind GLP-1RAs

GLP-1 receptor agonists activate GLP-1 receptors found throughout the body, including in reward-related regions of the brain. Preclinical studies suggest these drugs can reduce both the intake of and desire for addictive substances. That evidence has prompted researchers to ask whether the same mechanisms that curb appetite and moderate blood sugar might also dampen cravings for alcohol, nicotine, and other substances.

Real-world data from electronic health records has strengthened the case. A nationwide study using US Department of Veterans Affairs data found that diabetic patients who took GLP-1RAs had a lower risk of developing substance use problems than those on other antihyperglycaemic drugs. A separate analysis across 136 US healthcare systems found that patients with opioid use disorder or alcohol use disorder who took GLP-1 receptor agonists had significantly lower rates of opioid overdose and alcohol intoxication.

For cannabis use disorder, a retrospective cohort study found that patients with obesity who used semaglutide had a reduced risk of both new-onset cannabis use disorder and relapse. Researchers compared the results with patients on non-GLP-1RA anti-obesity medications and found a clear difference.

Early Trial Results Are Mixed but Encouraging

Two completed trials for alcohol use disorder have published results. Both offer suggestive rather than definitive findings.

The EXALT trial tested exenatide against a placebo in people with alcohol dependence. It found no statistically significant reduction in heavy drinking days overall. Brain imaging told a different story. The exenatide group showed reduced activation in reward-related areas of the brain in response to alcohol cues, as well as lower dopamine transporter availability. In a subgroup of participants with obesity, the exenatide group also showed significantly reduced heavy drinking and alcohol intake compared to placebo.

A separate trial of low-dose semaglutide for alcohol use disorder reported medium to large effect sizes for grams of alcohol consumed and peak breath alcohol concentration. Semaglutide did not affect average drinks per day or the total number of drinking days. It did significantly reduce drinks per drinking day and weekly alcohol craving.

For nicotine and tobacco use disorder, a completed exenatide trial found participants were more likely to achieve smoking abstinence compared to those on placebo. Exenatide also reduced end-of-treatment craving among those who stopped smoking. A dulaglutide trial, by contrast, found no significant difference in abstinence rates.

Significant Gaps Remain in GLP-1RA Research

The review’s authors are direct: the overall number of trials is too low. Research is not keeping pace with the scale of the problem. Substance use disorders contribute substantially to rates of overdose death, alcohol-related disease, infectious disease, suicide, and accidental injury.

No US Food and Drug Administration-approved treatments exist for methamphetamine, cocaine, or cannabis use disorder. That gap makes the shortage of GLP-1RA trials in these areas particularly concerning.

“While GLP-1RAs may represent a paradigm shift for treating substance use disorder, current trials have focused on alcohol and nicotine/tobacco use disorders, with notable gaps for methamphetamine and cannabis use disorders,” the authors wrote.

The review also flagged a lack of consistency in trial design and measurement. Body mass index thresholds for eligibility varied widely across studies, with some excluding participants of normal or low weight entirely. Many people affected by substance use disorders are not overweight, raising questions about how broadly findings from these trials will apply.

What Comes Next for GLP-1 Receptor Agonist Trials

The authors call for trials that use harmonised endpoints, meaning outcomes that align with FDA regulatory guidance. The FDA has published specific frameworks for evaluating treatments for opioid use disorder and stimulant use disorder. Researchers also need to study next-generation GLP-1 receptor agonists, including oral formulations that may be easier to access than the injections used in almost all ongoing trials.

One notable development arrived after the review closed. In November 2025, researchers registered two large Phase 3 trials for brenipatide, a novel dual GLP-1 and GIP receptor agonist. Each trial aims to enrol around 1,100 participants with moderate to severe alcohol use disorder. That makes them the most substantial investment in GLP-1RA research for addiction to date. A smaller trial is also examining whether brenipatide can help people who recently quit smoking stay quit.

Whether GLP-1 receptor agonists will prove transformative for substance use disorders remains an open question. What the evidence clearly shows is that the scientific community is taking it seriously. The next several years of trials will produce answers with consequences for public health policy well beyond the diabetes clinic.

Source: dbrecoveryresources