GLP-1s Proving to Be Effective in Treating Substance Use Disorder

In my last blog, I wrote that psychedelics were the next frontier in substance use disorder (SUD) treatment. Certainly as we look at the current landscape and how it is poised to affect the future, the notion has merit. But there’s another drug category – Glucagon-like peptide-1s, or GLP-1s – that we could include in that category.

GLP-1s may be all the rage today in weight loss, but evidence is mounting that they are an effective medication at treating substance use disorder (SUD) and other addictions as well.

Glucagon-like peptide-1 (GLP-1) is a hormone naturally created by the small intestine that triggers insulin release from the pancreas, manages blood sugar levels, slows stomach emptying during digestion, increases satiety (feeling of fullness) after eating, and controls appetite.

The success of popular medications (e.g. Ozempic, Wegovy) that mimic this hormone in managing diabetes and weight loss is well-documented. Their off-label use for treating SUD may be less known, but positive early results in retrospective research and pilot programs demand a closer look.

The great potential GLP-1s hold isn’t surprising, given how they work in the body, especially as it relates to their role in influencing the release of dopamine in the part of the brain linked to motivation, pleasure, and reward. The physiologic explanation for opioid use disorder, for example, centers on the large release of dopamine in response to opioid use, the brain’s reduction in the natural production of dopamine over time as a result of prolonged use, and the subsequent need to continue using opioids to achieve the same effect. A medication that can reduce those cravings for opioids—or other addictive substances, including food, alcohol, or nicotine—is promising as a treatment for addiction.

In April, at this year’s National Council for Mental Wellbeing Conference in Denver, Dr. Steven Klein, an addiction medicine physician and scientist with Caron in Pennsylvania, presented to the National Council’s SUD Committee on Caron’s work in treating patients with GLP-1s. At the time, Caron had treated 442 patients in its residential or partial hospitalization programs. The majority (64 percent) were treated for alcohol use disorder. Five percent had been treated for OUD, and just over 5 percent had been treated for cocaine use disorder. Those with a variety of other disorders, including stimulant and polysubstance use, made up the rest of the cohort.

Using the WHO-5 Well-Being Index as one measure, mean percentage scores for a subgroup of the Caron patients went from a baseline of 27 to 71 over eight months, indicating a person's subjective mental well-being and quality of life have improved. Over the same timeframe, using the Penn Alcohol Craving Scale (PACS), cravings to drink alcohol decreased from 20.3 to 6.

Other outcomes measures at Caron showed retention in treatment for OUD to be 94 percent at one month for those being treated with a GLP-1 versus 69 percent for those receiving traditional OUD treatment, and 84 percent at three-months versus 50 percent for those who were not receiving a GLP-1.

Multiple retrospective studies have also shown promising results, including: a 50 percent decrease in new alcohol use disorder (AUD) diagnoses and relapse; decreased alcohol-related hospitalizations; a 50 percent reduction in alcohol intoxication events; a 42 to 68 percent reduction in opioid overdose risk; and a 40 percent reduction in overdose events.

In the first-ever study to directly compare GLP-1s head-to-head against all three US Food and Drug Administration-approved AUD medications, those using a GLP-1 had a 45 percent lower AUD relapse rate. At the same time, multiple clinical trials are under way at various phases.

The Center for Addiction Science, Policy and Research (CASPR) is central to many of the pilot programs taking place, including those at Caron. In fact, the organization is planning a major study of 1,200 individuals in Pittsburgh, in partnership with the Department of Human Services in Allegheny County. This study will measure the impact of GLP-1s on alcohol and opioid use, as well as economic and social outcomes including recidivism and employment.

Those who have publicly spoken about their SUD struggles and experience with GLP-1s cite its ability to reduce or eliminate cravings, even in the face of the strongest temptations. But for many people, the challenge in getting the medication is cost. Because the drugs are not FDA-approved to treat SUD, they are used off-label, meaning insurance does not cover them for that purpose, putting the out-of-pocket cost out of reach for the Medicaid population, for example. CASPR is working to change that. Its mission is to bring better addiction medicines to market – high impact treatments that can reduce the rates of addiction at a population scale.