We have commented previously about the amazing science that can be done using data collected by a nationwide healthcare system, which the United States lacks. The result is that we are guessing, with tiny sample sizes, rather than knowing with mammoth sample sizes extending deep into the past.

Case in point is a study of GLP-1 receptor agonists to treat alcohol use disorder (AUD) in Sweden. Researchers were able to analyze the anonymized records of 227,866 Swedes with a diagnosis of AUD from 2006-2023. Overall, 6,276 of those patients had received prescriptions for GLP-1 drugs for diabetes and/or overweight. The median follow-up time was 8.8 years. 

Researchers found:

• 133,210 (58.5%) experienced at least one hospitalization for AUD
• Users of semaglutide had two-thirds (64%) of the average rate of hospitalization
• Users of liraglutide had three-quarters (72%) of the average rate of hospitalization
• Users of other medications had a slightly lower (90%) average rate of hospitalization

GLP-1 drugs prescribed in the study included exenatide, liraglutide, dulaglutide, and semaglutide. Other AUD drugs prescribed included disulfiram, acamprosate, and naltrexone. The six researchers, all associated with hospitals in Sweden and Finland, came to this hopeful conclusion:

Among patients with AUD and comorbid obesity/type 2 diabetes, the use of semaglutide and liraglutide [was] associated with a substantially decreased risk of hospitalization due to AUD. This risk was lower than that of officially approved AUD medications.

A much smaller study (83,825 patients) with a much shorter follow-up time (12 months) in the U.S. found a significant reduction in relapse during treatment for alcohol use disorder for patients prescribed GLP-1 drugs for obesity. The study was conducted by researchers at the Center for Science, Health, and Society at Case Western Reserve University School of Medicine in Cleveland, Ohio, and co-authored by Nora D. Volkow, Director of the National Institute on Drug Abuse (NIDA). The bottom line:

[S]emaglutide compared with other anti-obesity medications is associated with a 50%-56% lower risk for both the incidence and recurrence of alcohol use disorder for a 12-month follow-up period.

The Case Western study, unlike the Swedish study, delves into the reasons that GLP-1 drugs are impacting both AUD incidence and recurrence. The researchers say the GLP-1 drugs “likely” impact the dopamine reward system in the brain. The authors note, “Importantly the rewarding effects of food are a main contributor to overeating and obesity, just as the rewarding effects of alcohol drive alcohol consumption.”

Other possible ways GLP-1 drugs impact AUD, according to researchers, is that they “mediate stress responses.” Researchers only mention the involvement of the gut in passing, as a “peripheral mechanism” that may impact alcohol absorption rates, which “could make alcohol less rewarding.”

The Case Western paper references a study of people diagnosed with Type 2 diabetes and their incidence of AUD diagnosis. Interestingly, researchers found the same rate of reduced incidence of AUD in diabetics as in those with obesity. But they also found the same rate of reduced incidence of AUD in Type 2 diabetics who had not been diagnosed with obesity. There are almost no studies of GLP-1 drugs on normal-weight individuals.

Again, the researchers come to a firm conclusion:

[O]ur study provides real-world evidence supporting the therapeutic benefits of semaglutide for AUD.

GLP-1 drugs are not a magic remedy for AUD, but the results of these studies show clearly the need for more randomized controlled trials, some of which are taking place now. The use of GLP-1 drugs for diabetes and overweight, and the potential for moderating addictive behaviors including opioid use disorder and AUD, warrant further investigations of exactly how the drugs work. In particular, researchers may need to lower their gaze from the brain to the gut to understand how GLP-1 drugs affect addiction.

Written by Steve O’Keefe. First published January 13, 2025.

Sources:

“Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder,” JAMA Psychiatry, November 13, 2024.

“Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population,” Nature Communications, May 28, 2024.

Image Copyright: georgerudy.