In a recent study published in Nature communicationsresearchers investigated the potential therapeutic benefits of semaglutide for alcohol use disorders (AUDs).
Record
AUDs are a global health problem, but current treatment options are limited. The discovery of new drugs to treat AUD is vital, given recent evidence of reduced alcohol intake in people prescribed glucagon-like peptide-1 receptor agonist (GLP-1RA) drugs for type 2 diabetes or obesity.
Semaglutide is a GLP-1 receptor agonist approved to treat type 2 diabetes in 2017 and to reduce obesity in 2021 and has been found to reduce alcohol consumption and relapse in rats. However, research on the therapeutic advantages of semaglutide in the prevention and treatment of AUD in the real world remains insufficient.
About the study
In the present multicenter study, investigators investigated the relationship between semaglutide and the onset and recurrence of AUD in obese subjects. They then assessed the repeatability of the study’s findings among patients with type 2 diabetes from different time periods.
The team compared type 2 diabetes patients with obesity (33%) and diabetics who were not obese (67%) with obese patients diagnosed with type 2 diabetes (40%) and people with obesity but no diagnosis of diabetes (60%) , to investigate potential interactions of the effects of semaglutide use among individuals with the two comorbidities.i
Outcomes were assessed independently by age, sex, and race. Researchers analyzed electronic medical records obtained from 83,825 obese subjects with semaglutide or non-GLP-1 receptor agonist antiobesity drug prescriptions between June 2021 and December 2022. They included patients with at least one obesity-related comorbidity, excluding those who had previously received different GLP-1RAs or underwent bariatric surgery.
The researchers divided the study population into three groups: semaglutide (45,797 patients), non-GLP1-RA anti-obesity drug (38,028 patients), and naltrexone/topiramate (16,676 patients). They included the naltrexone/topiramate cohort to evaluate semaglutide and naltrexone/topiramate for the risk of AUD in obese subjects.
To investigate the relationship between semaglutide and AUD in patients with type 2 diabetes, researchers divided participants into two groups: those prescribed semaglutide (n=25,686) and those prescribed antidiabetic drugs GLP-1 receptor agonists (n= 573.117). . They evaluated the relationship between semaglutide and recurrent AUD in 22,113 subjects (668 semaglutide recipients and 21,445 patients receiving non-GLP-1 agonist antidiabetic drugs).
Anatomical therapeutic chemical (ATC) codes for antidiabetic drug status that is not a GLP-1 receptor agonist. The researchers assessed the semaglutide and comparison groups on potential risk factors for AUDs, including demographics, socioeconomic determinants of health, lifestyle issues, preexisting medical conditions, medications, and types of medical visits. They also matched obesity subcategories to help manage obesity severity. They used Cox proportional hazard regression models to derive hazard ratios for analysis.
Results and discussion
Compared with other antiobesity drugs, semaglutide was associated with a 50%–56% reduced risk of both incident (0.4% vs. 0.7%; hazard ratio, 0.5) and recurrence of alcohol use disorder during one year after- until period. The team found similar results among 598,803 people with type 2 diabetes. Semaglutide significantly reduced the incidence of AUDs than naltrexone or topiramate (0.4% vs. 0.8%, hazard ratio 0.4).
Compared with anti-obesity drugs that are not GLP-1 receptor agonists, semaglutide significantly reduced AUD recurrence (23% vs. 43%; hazard ratio, 0.4). Compared with topiramate or naltrexone, semaglutide reduced the incidence of AUD (22% vs. 60%; hazard ratio, 0.3). Compared with non-GLP-1 receptor agonist antidiabetic drugs, semaglutide was associated with a significantly reduced likelihood of AUD (0.3% vs. 0.5%; hazard ratio, 0.6).
Compared with antidiabetic drugs of the non-GLP-1 receptor agonist type, semaglutide significantly reduced the likelihood of AUD recurrence (23% vs. 33%; hazard ratio, 0.6). The team observed significantly reduced risks in people with or without a diagnosis of obesity. Results were consistent across sex, age, race, and type 2 diabetes status. The significantly reduced risk associations of semaglutide medication with AUD incidence and recurrence were maintained, although somewhat attenuated, during two-year and three-year follow-up.
Semaglutide could reduce AUD diagnosis and relapse by altering the brain’s dopamine reward system through GLP-1 receptors in the ventral regions and nucleus accumbens. This reward system regulates food and alcohol consumption, which leads to overeating and obesity. The anti-inflammatory properties of semaglutide have also contributed to potential benefits for AUD. Previous randomized trials found significant reductions in brain activity to alcohol cues, fewer heavy drinking days, and reduced total alcohol intake in AUD patients with obesity.
conclusion
The study findings showed that semaglutide could reduce AUD incidence and recurrence in obese subjects and patients with type 2 diabetes, supporting further randomized clinical research to accelerate its clinical use for AUD. Future research should investigate interactions of semaglutide with alcohol and AUD medications and longer-term relationships in obese patients.
