The VA Launches Trial Testing Semaglutide for Alcohol Use Disorder in Veterans
Semaglutide, also known by the famous brands Ozempic and Wegovy, is already used for conditions such as diabetes and weight management. Now, the Department of Veterans Affairs is studying it to see whether it can also help Veterans with alcohol use disorder (AUD).
The VA Office of Research and Development is leading a Phase 3 clinical trial called CRAVE, short for Cessation or Reduction of Alcohol Consumption in Veterans. The study will compare semaglutide for alcohol use disorder with a placebo in Veterans with moderate or severe AUD.
The clinical trial has launched because there is a clear need for more treatment options.
According to VA trial records, more than 400,000 Veterans receiving VA care have been diagnosed with AUD. Yet, only about 40,000 were receiving medication treatment for it, based on VA data cited when the study was designed.
CRAVE will examine whether semaglutide can safely reduce risky drinking among Veterans with moderate or severe AUD. It will also give the VA a chance to learn how the treatment works among Veterans who may already be dealing with other mental health concerns or receiving psychiatric care.
Dr. Dave Oslin, Principal Investigator for the CRAVE Trial and Chief of Behavioral Health, Philadelphia VA Medical Center, says,
“VA's experience treating Veterans with several health needs at once puts the system in a strong position to study those questions.”
Here’s what the CRAVE trial is testing, how it will work, and what the results could mean for future AUD treatment.
What Is the CRAVE Trial?
CRAVE is a randomized, placebo-controlled Phase 3 trial studying semaglutide in Veterans seeking treatment for moderate or severe AUD.
Veterans who qualify will be randomly assigned to receive either semaglutide or placebo injections. The treatment period lasts 24 weeks and is followed by a four-week safety follow-up. In addition to that, study visits are planned every four weeks.
Participants receiving semaglutide will start at 0.25 milligrams per week for the first four weeks. The dose can then increase bit by bit up to a maximum of 2.4 milligrams per week. That, however, depends on how well the participant tolerates it.
The study is designed so that the participant, care provider, investigator, and person assessing the outcomes don’t know if the participant received semaglutide or the placebo.
The Trial Is Looking at Reduced Drinking, and Not Just Abstinence
One important part of CRAVE is how researchers will determine whether the treatment works. The main outcome also isn’t simply whether a Veteran stops drinking altogether.
Instead, researchers will look for at least a two-level drop in the World Health Organization's risk drinking level from where a participant started. The drinking-risk levels used in the study include low, moderate, high, and very high. Moving from very high risk to moderate risk, for example, would count as a two-level improvement.
Dr. Oslin said the decision to focus on reduced drinking was made with the FDA.
“According to the FDA, there are three acceptable outcomes for approving treatments for alcohol use disorder,” he said. “Total abstinence is one of the outcomes.”
He said FDA also considers reduced risky drinking and the absence of heavy drinking days as potential outcomes for an AUD treatment.
“For this trial, in consultation with FDA, we have chosen a reduction of heavy drinking,” he added.
The primary outcome is the two-level reduction in WHO risk drinking level. Researchers will also track whether participants have no heavy drinking days as a secondary outcome. The study will measure drinking through the Timeline Follow-Back method, which asks participants to report their daily alcohol use over a set period.
This gives researchers more than one way to measure improvement. A Veteran may not stop drinking completely but could still show a meaningful drop in alcohol use.
Why Is VA Studying a GLP-1 for Alcohol Use Disorder?
Semaglutide belongs to a group of medicines called GLP-1 receptor agonists. These drugs are already commonly used for diabetes and weight management. Researchers are now studying whether a GLP-1 for alcohol use disorder could also help reduce drinking.
The VA Office of Research and Development says CRAVE was developed after promising findings from earlier clinical experience, retrospective research, preclinical studies, and pilot clinical trials.
The Phase 3 study is meant to provide stronger evidence about whether semaglutide works better than a placebo for AUD.
More treatment choices could make a difference.
The ORD notes that fewer than 2% of U.S. adults with AUD receive medication treatment in a given year. The study record also says there has not been a new FDA-approved medication for alcohol use disorder in nearly two decades.
That doesn’t mean semaglutide has already been proven to work for AUD. And that is why CRAVE is being conducted: to answer that question.
Veterans With AUD May Also Have Other Mental Health Needs
For some Veterans, alcohol use disorder is not the only health concern they are managing. Dr. Oslin said Veterans with AUD often live with other mental health conditions as well.
“VA’s clinical care and research is especially focused on the complexities these comorbidities involve,” he said. “Our experience treating Veterans is why VA is uniquely positioned to conduct this trial.”
CRAVE is not mainly designed to test semaglutide as a treatment for PTSD in Veterans, as well as depression and other mental health conditions.
However, researchers will look at whether the drinking outcomes differ among participants who already have a psychiatric condition. They will also look at Veterans who are already receiving psychiatric medications or psychotherapy when they enter the study.
Dr. Oslin said these other conditions will be measured during the trial.
“While the trial is not primarily designed to specifically address these additional mental health conditions, we will be examining the effects of these comorbidities on outcomes,” he said.
Researchers will also look at whether any of those conditions improve as a secondary effect. The main goal, however, remains clear. It’s to find out if semaglutide can safely help Veterans with moderate or severe AUD reduce risky drinking.
Primary Care Could Play a Larger Role
Another question is where semaglutide could fit into Veteran care if CRAVE is successful.
AUD treatment is often connected with addiction or specialty mental health programs. But Dr. Oslin said many people with AUD never seek treatment through those programs.
“Most individuals with AUD never seek treatment in a specialty mental health program,” he said. “This is true for Veterans as well.”
Instead, primary care is often where these are first discussed.
“Primary care providers in the U.S. and in VA are the starting point for most mental health care, including addiction,” he added.
That could matter if a GLP-1 for alcohol use disorder eventually becomes an approved treatment.
Primary care providers already have experience evaluating patients and starting GLP-1 treatment for other conditions.
“Primary care providers are well poised to evaluate and initiate treatment with GLP-1s,” Dr. Oslin said. “So, providing new, evidence-based medicine for primary care providers makes sense.”
The VA also has an integrated health system where Veterans can be connected with mental health, substance use, pharmacy, and other services when they need more support.
“In the VA, with our large integrated health system, additional services beyond primary care are available to Veterans to support them in their own efforts to overcome the significant challenges of substance abuse and addiction,” he said.
Semaglutide would not replace those services. Instead, it could become another treatment option if the evidence supports its use.
Who Could Take Part In the CRAVE Trial?
Not every Veteran with alcohol use disorder will qualify for CRAVE. The study lists several basic requirements. Participants must:
- Be a Veteran.
- Be between 18 and 80 years old.
- Have a high or very high WHO risk drinking level before screening.
- Have a current diagnosis of moderate or severe alcohol use disorder.
- Be able and willing to provide informed consent.
The study also has a longer list of medical, psychiatric, medication, and safety requirements that the research team will review before enrollment. For example, some Veterans currently taking medications for AUD, including naltrexone, acamprosate, disulfiram, or topiramate, may not qualify if they used them within 30 days before randomization.
Current use of certain GLP-1 or glucose-lowering medications can also affect eligibility. Veterans shouldn’t stop taking any medication on their own to try to qualify for the study. The CRAVE research team will determine eligibility based on the full study criteria.
What Happens After the Trial Treatment?
CRAVE includes 24 weeks of treatment followed by a four-week safety follow-up.
The study is designed to show if the medication is safe and effective for Veterans with AUD during that period. It’s not meant to determine if someone who responds well to semaglutide would need to stay on it long term.
Dr. Oslin also said longer studies would be needed to answer that.
“This trial is designed to establish the safety of GLP-1s in this population and the efficacy over six months,” he said.
“Longer-term studies will be required to address the need for continued treatment,” Dr. Oslin added.
He also noted that other research has shown that the longer a person maintains reduced drinking, the more likely that new pattern may last.
Still, CRAVE will not answer every question about long-term treatment.
What Happens If Semaglutide Works?
A successful clinical trial would still be one step in a longer process.
The study currently lists an estimated primary completion date of April 28, 2028, and an estimated overall completion date of May 26, 2029. Those dates can change as the study moves forward.
The trial record also says de-identified study data may be shared with the FDA and Novo Nordisk for medication approval.
Dr. Oslin stated that the experience of running CRAVE should also help VA identify any practical problems that could come with using semaglutide for AUD.
“The results of the trial and experience we gain with the trial will provide a view into any barriers,” he said.
Those lessons could become important if the treatment eventually moves from research into regular clinical care. Even if the FDA approves semaglutide for alcohol use disorder, VA would still review the evidence before deciding whether and how to offer it to Veterans.
“If FDA approves, VA will evaluate the clinical evidence to see whether the treatment could become available to Veterans with AUD,” Dr. Oslin added.
For now, semaglutide remains an investigational treatment for AUD.
What the CRAVE Trial Could Add to Veteran Care
CRAVE is testing if semaglutide for alcohol use disorder can safely help Veterans. Researchers will also look at how the treatment works in Veterans with psychiatric conditions or those already receiving mental health care.
Primary care may also become an important part of that picture. As Dr. Oslin noted, many people with alcohol use disorder never enter specialty addiction treatment.
If CRAVE is successful, semaglutide could eventually become another treatment option for Veterans with AUD.
VA Ann Arbor Health Care and the Orlando VA Healthcare System were contacted for additional information about the trial and its local implementation. Their public affairs teams acknowledged the inquiries, but no additional response was received by the publication deadline.
As the trial moves forward, the results will help determine if semaglutide can become another treatment option for Veterans who have alcohol use disorder.
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BY ALLISON KIRSCHBAUM
Veteran, Military History & Culture Writer at VeteranLife
Navy Veteran
Allison Kirschbaum is a Navy Veteran and an experienced historian. She has seven years of experience creating compelling digital content across diverse industries, including Military, Defense, History, SaaS, MarTech, FinTech, financial services, insurance, and manufacturing. She brings this expertis...
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Allison Kirschbaum is a Navy Veteran and an experienced historian. She has seven years of experience creating compelling digital content across diverse industries, including Military, Defense, History, SaaS, MarTech, FinTech, financial services, insurance, and manufacturing. She brings this expertis...
