By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Jun 14 2024

In a recent study published in Nature Communications, researchers investigated the potential therapeutic benefits of semaglutide for alcohol use disorders (AUDs).

Study: Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. Image Credit: Caroline Ruda/Shutterstock.comBackground

AUDs are a global health problem, but current treatment options are limited. The discovery of novel drugs to treat AUD is crucial, given recent evidence of reduced alcohol intake in individuals prescribed glucagon-like peptide-1 receptor agonist (GLP-1RA) drugs for type 2 diabetes or obesity.

Semaglutide is a GLP-1 receptor agonist authorized for diabetes type 2 treatment in the year 2017 and reducing adiposity in 2021 and has been found to reduce alcohol consumption and relapse in rats. However, research on the therapeutic advantages of semaglutide in preventing and treating AUD in the real world remains inadequate.

About the study

In the present multicentre study, researchers investigated the relationship between semaglutide and AUD occurrence and recurrence in obese individuals. They then evaluated the repeatability of the study findings among type 2 diabetes patients from different periods.

The team compared type 2 diabetes patients with adiposity (33%) and diabetics who were not obese (67%) with obese patients diagnosed with type 2 diabetes (40%) and individuals with obesity but no diabetes diagnosis (60%), to investigate potential interactions of semaglutide use effects among individuals with the two comorbidities.i

The outcomes were assessed independently by age, gender, and race. Researchers analyzed the electronic medical records obtained from 83,825 obese individuals with semaglutide or non-GLP-1 receptor agonist anti-obesity drug prescriptions between June 2021 and December 2022. They included patients with at least one obesity-related comorbidity, excluding those who had previously taken different GLP-1RAs or undergone bariatric surgery.

The researchers separated the study population into three groups: semaglutide (45,797 patients), non-GLP1-RA anti-obesity medicine (38,028 patients), and naltrexone/topiramate (16,676 patients). They included the naltrexone/topiramate cohort to assess semaglutide and naltrexone/topiramate for incident AUD risk in obese individuals.

To investigate the relationship between semaglutide and AUD in type 2 diabetic patients, the researchers divided the participants into two groups: those prescribed semaglutide (n=25,686) and those prescribed non-GLP-1 receptor agonist anti-diabetic medications (n=573,117). They evaluated the link between semaglutide and recurrent AUD in 22,113 individuals (668 semaglutide recipients and 21,445 patients on non-GLP-1 receptor agonist anti-diabetes medicines).

Anatomical therapeutic chemical (ATC) codes ascertained non-GLP-1 receptor agonist anti-diabetic medicine status. The researchers evaluated the semaglutide and comparative groups concerning possible risk factors for AUD, such as demographics, socioeconomic health determinants, lifestyle issues, pre-existing medical conditions, medicines, and medical visit types. They also matched obesity sub-categories to help manage obesity severity. They used Cox proportional hazard regression models to derive the hazard ratios for analysis.

Results and discussion

Compared with other anti-obesity drugs, semaglutide was related to a 50%–56% decreased risk of both the incidence (0.4% vs. 0.7%; hazard ratio, 0.5) and recurrence of alcohol use disorder throughout a one-year follow-up period. The team noted similar results among 598,803 type 2 diabetes individuals. Semaglutide considerably reduced the incidence of AUD incidence than naltrexone or topiramate (0.4% vs. 0.8%; hazard ratio, 0.4).

Compared with non-GLP-1 receptor agonist anti-obesity drugs, semaglutide considerably decreased AUD recurrence (23% vs. 43%; hazard ratio, 0.4). Compared to topiramate or naltrexone, semaglutide reduced the incidence of AUD incidence (22% vs. 60%; hazard ratio, 0.3). Compared to anti-diabetic medications of non-GLP-1 receptor agonist type, semaglutide was related to a considerably decreased probability of AUD incidence (0.3% vs. 0.5%; hazard ratio, 0.6).

Compared to anti-diabetic medications of non-GLP-1 receptor agonist type, semaglutide considerably reduced AUD recurrence probability (23% vs. 33%; hazard ratio, 0.6). The team noted significantly decreased risks in individuals with or without an obesity diagnosis. Results were consistent across biological sex, age, race, and type 2 diabetes status. The considerably decreased risk correlations of semaglutide medication with AUD incidence and recurrence were maintained, albeit somewhat reduced, at the two- and three-year follow-ups.

Semaglutide could reduce AUD diagnosis and recurrence by altering the brain's dopamine reward system through GLP-1 receptors in the ventral tegmental regions and nucleus accumbens. This reward system regulates food and alcohol consumption, which leads to overeating and obesity. Semaglutide's anti-inflammatory properties have also contributed to potential advantages for AUD. Previous randomized trials found significantly reduced brain activity to alcohol cues, lower heavy drinking days, and reduced overall alcohol intake in AUD patients with obesity.

Conclusion

The study findings showed that semaglutide could reduce AUD incidence and recurrence in obese individuals and type 2 diabetic patients, supporting further randomized clinical research to accelerate its clinical usage for AUD. Future research should explore semaglutide interactions with alcohol and AUD medications and longer-term relationships in obese patients.

Journal reference:

Wang, W., Volkow, N.D., Berger, N.A., et al., Associations of semaglutide with the incidence and recurrence of alcohol use disorder in the real-world population. Nat Commun 15, 4548 (2024). doi: https://doi.org/10.1038/s41467-024-48780-6