Vanderbilt Launches Clinical Trial Testing Tirzepatide as Adjunct to Buprenorphine for Opioid Use Disorder

Vanderbilt Health has opened enrollment for a national clinical trial testing whether tirzepatide, a glucagon-like peptide-1 receptor agonist already approved for diabetes and weight management, can help prevent relapse in people receiving treatment for opioid use disorder. The study, known as TAB (Evaluation of Tirzepatide as an Adjunct to Buprenorphine for the Treatment of Opioid Use Disorder), represents one of the first randomized controlled trials to examine GLP-1 medications as a potential tool in addiction medicine.

The double-blind, placebo-controlled trial is being conducted through the National Institute on Drug Abuse's Clinical Trials Network and will recruit participants at multiple sites across the country. At Vanderbilt, researchers hope to enroll approximately 31 participants who have started buprenorphine treatment within the past 80 days and have moderate to severe opioid use disorder.

How the study works

Participants in the six-month trial will receive weekly injections of either tirzepatide or a placebo while continuing their buprenorphine regimen. They will also wear Fitbit devices to track sleep data and receive cell phones to facilitate data collection. Study participants will be compensated for their time and travel.

"There is a critical need to address treatment options for all individuals with opioid use disorder," said Dr. Jessica Young, associate professor of clinical obstetrics and gynecology at Vanderbilt Health and principal site investigator for the study. "Opioid use disorder is a chronic disease where relapse is common. Finding ways to prevent relapse for both men and women is lifesaving."

Dr. Young also serves as medical director of Firefly, Vanderbilt's comprehensive care and treatment program for pregnant and postpartum women with substance use disorder and their children. While the Firefly program focuses on women, the TAB study will include both male and female participants.

The science behind GLP-1s and addiction

GLP-1 receptor agonists have emerged as one of the most significant medication classes in modern medicine, transforming treatment for type 2 diabetes and obesity. The drugs work by mimicking a hormone that regulates blood sugar and appetite. More recently, researchers have discovered that these medications may also affect brain reward pathways involved in addiction.

Previous observational studies have suggested that people taking GLP-1 medications for diabetes may experience reduced cravings for alcohol, nicotine, and other substances. A study published earlier this year in the BMJ found that veterans taking GLP-1 drugs had a 14 percent reduced risk of developing new substance use disorders compared to those taking other diabetes medications.

However, observational data cannot prove causation. The TAB study is designed to provide the randomized controlled evidence needed to determine whether tirzepatide genuinely helps prevent relapse in people with opioid use disorder.

The stakes in Tennessee

The trial arrives as Tennessee continues to grapple with one of the nation's most severe opioid crises. Approximately 2,500 people die from drug overdoses in the state each year, with opioids responsible for roughly 80 percent of those deaths. Opioid use disorder affects more than 2 million Americans nationwide, yet relapse remains common even among those receiving medication-assisted treatment.

Buprenorphine is one of three medications approved by the Food and Drug Administration for treating opioid use disorder, along with methadone and naltrexone. While these medications have proven effective at reducing overdose deaths and supporting recovery, many patients still struggle with cravings and eventually relapse. The TAB study aims to determine whether adding tirzepatide to buprenorphine treatment can improve outcomes.

"We hope to find that adding a GLP-1 to treatment plans will help people stabilize on buprenorphine therapies and prevent relapse," Young said. "This could change the standard of care if it improves outcomes and decreases relapse."

Expanding the addiction treatment toolbox

If the trial demonstrates efficacy, tirzepatide could become the first new pharmacological approach to opioid use disorder in years. The medication is already widely available and familiar to physicians, which could accelerate adoption if the data supports its use in addiction treatment.

The study also represents a broader shift in addiction medicine toward medications that target the neurological mechanisms of craving and reward. Researchers at the VA recently launched a similar trial testing semaglutide, another GLP-1 medication, for alcohol use disorder in veterans. Together, these studies could establish whether the GLP-1 class has a role to play across multiple types of addiction.

For those interested in participating in the Vanderbilt trial, researchers can be reached at 615-587-9669 or via email at vumc.ctn152tab@vumc.org. Eligible participants must be at least 18 years old, have moderate to severe opioid use disorder, and have started buprenorphine treatment within the past 80 days.

People seeking help for opioid addiction can find medication-assisted treatment programs nationwide through the SAMHSA treatment locator or by contacting their healthcare provider.