Evidence is growing that GLP-1 receptor agonists, the drugs best known for treating diabetes and obesity, could also have a role in addiction care.
A study published in March found that GLP-1 use was associated with 75% lower odds of any substance use disorder among adults with Type 2 diabetes or obesity. That included 74% lower odds of alcohol use disorder. In July, the VA launched a clinical trial that will enroll more than 600 veterans at 18 VA medical centers to test whether semaglutide can treat alcohol use disorder.
Providers are also moving forward. In September, Santa Fe, N.M.-based Quel Health launched a telehealth platform built around GLP-1s for addiction and named Wernersville, Pa.-based Caron Treatment Centers as a founding strategic partner. The platform builds on work at Caron’s Pennsylvania and Florida campuses, which have treated more than 600 patients with GLP-1 receptor agonists for substance use disorder.
Steven Klein, MD, PhD, co-founder and chief medical officer of Quel Health and chief medical innovation officer at Caron, told Becker’s about what the evidence shows so far, the biggest open questions and what health systems should consider before offering GLP-1s for addiction care.
Editor’s note: Responses were lightly edited for clarity.
Question: What do we know so far about GLP-1s for substance use disorders?
Dr. Steven Klein: There is a real signal, and it is strongest for alcohol. The animal work has been consistent for more than a decade: give a GLP-1 receptor agonist and alcohol intake drops, across species and across models. The retrospective human data point the same direction. When you look at large populations of people who were prescribed these medications for diabetes or weight, you see fewer alcohol-related outcomes than in similar patients on other medications, and that finding has now been reproduced in different health systems, different countries and with different endpoints. That reproducibility is what makes me take it seriously.
A single retrospective study can always be explained away. The same result showing up in different settings, different populations and with different outcome measures is much harder to dismiss, and it fits what we understand about how these drugs act on reward circuitry.
Then there is what we hear in the room. Patients on GLP-1s tell us they think about drinking less, that the pull isn’t there the way it used to be, and some say the same about other substances. That’s an anecdote, and I treat it as an anecdote, but we hear the same story over and over, and it’s what drew the media to this long before the field had a way to measure it. The first prospective [randomized controlled] trials are now starting to put numbers on what patients have been describing.
Q: What are the biggest unanswered questions?
SK: The one I think about most is what these medications do to the rest of treatment. At Caron we don’t prescribe a GLP-1 and send someone on their way. It’s one piece of a comprehensive plan that includes therapy, medical care, peer support, family work and everything else residential treatment is built on. Our working belief is that the medication helps all of that work better and last longer. Some have started calling this the “habit window”: If the drug quiets the drive to use, a patient may get a stretch of time where new routines, new coping strategies and new relationships can take root in a way they couldn’t when every day was a fight with craving. That is a hypothesis. It is a good one, and it matches what we see clinically, but nobody has tested it properly yet.
We also don’t know how long people should stay on treatment, or what happens when they stop. Is there a course of therapy after which the benefit holds, or does the craving come back the way weight does? We don’t have the follow-up yet. I’d point out that none of these questions are unique to addiction. Obesity medicine is wrestling with the exact same unknowns about duration and discontinuation, and the two fields are going to learn from each other.
Q: What should health systems keep in mind before offering GLP-1s for addiction care?
SK: Start with the obvious: As of today, every GLP-1 is off label for every substance use disorder. That shouldn’t scare anyone off. Off-label prescribing is routine across medicine, and addiction medicine in particular has a long history of it; several medications we use regularly for alcohol use disorder were never approved for that purpose. What it does mean is that the conversation with the patient has to be explicit. At Caron we built a dedicated informed consent process for GLP-1s. Patients hear what the data show, where the signal is strong and where it is thin, what the known risks are, and what we still don’t know. Then they decide. I think that model should travel with the medication wherever it goes.
The other thing to keep in mind is access. These are expensive medications, and for an addiction indication there is usually no insurance coverage, so more often than not the cost lands on the patient. That is a real limitation, and it needs to be part of the planning from the start rather than something a system discovers after the first prescription is written.
Q: Where do you see this heading in the next few years?
SK: I expect FDA approval of at least one GLP-1 for alcohol use disorder, and I wouldn’t be surprised if it’s several. The trials are underway, and the signal is strong enough that I think it holds up.
The approval isn’t the part I care about most, though. My best-case scenario is that this moment changes how we talk about addiction. For a long time the public conversation about drinking, drug use, obesity and compulsive behavior more broadly has really been a conversation about willpower and character. Then a diabetes drug comes along, and people who spent years white-knuckling it start reporting that the urge has quieted. That is hard to square with the idea that they were simply weak. It points to biology, to systems in the brain and body that can be shifted, and once you see it that way, blaming the individual starts to look pretty useless. If we can carry that understanding into how we build health systems, how we fund treatment and how we treat each other, we have a chance at something more durable than a new prescription. We could end up with a society that is set up to support each person’s health instead of judging them for struggling with it.
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