Low-dose semaglutide reduces alcohol consumption and cravings in early trial
Study finds significant reductions in drinks per drinking day and alcohol craving, with potential benefits for smoking reduction
A recent JAMA Psychiatry study investigates the effectiveness of semaglutide in reducing alcohol consumption and craving in adults with alcohol use disorder (AUD).
Alcohol use disorder and semaglutide
Every year, around 2.6 million deaths occur worldwide from alcohol use. It is causally linked with the incidence of over 200 medical and disability conditions. Many studies have also indicated that alcohol use increases the risk of common diseases, such as cardiovascular disease, liver disease, and cancers, which significantly contribute to mortality and morbidity rates.
Previous studies found that reduced alcohol intake may, irrespective of abstinence, improve health outcomes. In comparison to 2016-2017 estimates, alcohol-related liver disease has increased to 29% in 2020 in the US.
Although many adults meet the criteria for AUD, only a few receive treatment or pharmacotherapy. AUD medications are underutilized due to limited awareness of these medications, barriers related to stigma, and less Food and Drug Administration (FDA)–approved therapies.
The FDA approved semaglutide to treat diabetes in 2017 and obesity in 2021. Interestingly, a rapid surge in semaglutide use was simultaneously accompanied by reports of reduction in alcohol use and craving during treatment. This observation highlighted the potential role of semaglutide in the voluntary reduction of alcohol consumption and cravings.
Considering the preclinical study findings that revealed semaglutide leads to a reduction in alcohol intake, there is an urgent need to conduct clinical trials to validate the results.
About the study
The current phase 2 randomized clinical trial, conducted at the University of North Carolina (UNC)-Chapel Hill School of Medicine, assessed the effect of once-weekly subcutaneous semaglutide on non-treatment-seeking adults with AUD. This study followed a hybrid design that combined clinical outpatient and human laboratory components.
The outpatient segment involved nine weeks of treatment with either semaglutide or placebo and the effect of the treatments were evaluated in the 10th week. Objective laboratory alcohol self-administration was evaluated at pre-treatment, i.e., prior to the first week and between weeks 8 and 9. The treatment group received 0.5 mg of semaglutide per week.
All participants were between 21 and 65 years of age. Women consuming more than seven and men consuming more than fourteen alcoholic drinks in a week with two or more heavy drinking episodes were considered to have AUD.
Individuals with a history of using GLP-1 receptor agonists, currently seeking treatment for alcohol-related problems, and actively attempting to reduce alcohol consumption were excluded. Furthermore, diabetic individuals or those with neurological illnesses were excluded from the study.
Before one week of semaglutide initiation, the selected participants underwent a pre-treatment alcohol self-administration session. They were subjected to either semaglutide or placebo treatment for 2-9 weeks, followed by a post-treatment alcohol self-administration session that was scheduled for weeks 8 and 9.
The primary outcome was based on two lowest semaglutide dose sequences, i.e., 0.25 mg/week for weeks 1-4 and 0.5 mg/week for weeks 5-8. However, the week 9 dose was flexible and could be as high as 0.5 mg, which helped researchers understand the safety and tolerability of semaglutide at a higher dose.
A standard protocol was used to estimate voluntary alcohol consumption and the ability to delay drinking. Here, participants were provided with a beverage of their choice, and the amount of alcohol consumed was measured in grams using anthropometric formulas based on a pre-specified maximum breath alcohol concentration (BrAC) limit. BrAC was measured every 30 minutes of drinking. Estimated volume consumed (g-ETOH) and peak BrAC were considered as co-primary outcome measures.
Study findings
A total of 48 individuals participated in this study, of which 34 were female, and 14 were male. On average, the participants exhibited moderate AUD severity.
The mean age of the participants was 39.9 years, and the majority of participants had body mass index (BMI) greater than 30. Out of 48 participants, 42 completed outpatient visits through week 9. It must be noted that those participants who completed post-treatment alcohol sessions received the required four doses at 0.5 mg/week.
In comparison to placebo, semaglutide treatment exhibited a reduction in post-treatment laboratory consumption with a medium to large effect size for grams of alcohol consumed and peak breath alcohol concentration. Although treatment conditions failed to predict the duration of delay time or extent of drinking or abstinence in the self-administration task, it indicated that semaglutide treatment could considerably reduce weekly cravings and decrease the number of drinks per day.
The medication effect improved considerably during weeks 5 to 8, compared to the first four weeks. In the semaglutide group, the number of zero heavy drinking days increased significantly from weeks 1 through 8. No serious adverse effect was observed in the treatment group.
Conclusions
The current study indicated that weekly once semaglutide treatment could effectively reduce alcohol cravings and consumption rates among adults with AUD. A larger clinical trial is required to assess the efficacy of other GLP-1RA and incretin therapies for AUD.
