Patients with obesity who received semaglutide had a 50%-56% lower risk for both the incidence and recurrence of alcohol use disorder (AUD) for a 12-month follow-up period, compared with other anti-obesity medications, according to the outcomes of a retrospective cohort study headed by Case Western Reserve University School of Medicine, Cleveland, OH. The consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without type 2 diabetes.
“The underlying mechanisms have not been fully delineated but are likely to involve modulation of the brain dopamine reward system via GLP-1 receptors, which are present both in the ventral tegmental areas (VTA), where dopamine neurons are located, and in the nucleus accumbens (NAc), which is the main projection of VTA dopamine neurons,” they authors write. “The involvement of the dopamine reward pathway in modulating food and alcohol consumption could explain why semaglutide is beneficial in reducing food consumption and in animal models reducing alcohol and other drug consumption.”
Following recent anecdotal reports and a series of small studies of reduced drinking in people being treated with glucagon-like peptide-1 receptor agonist (GLP-1RA) medications for T2DM or obesity, there is a significant interest in the potential of these medications for treating AUD.
Therefore, investigators from Case Western sought to examine the clinical benefits of semaglutide for AUD prevention and treatment, specifically in real-world populations as reported data is still very limited. Utilising a large database of patient electronic health records (EHRs), they conducted a nationwide multi-centre retrospective cohort study to assess the association of semaglutide with both the incidence and recurrence of AUD in individuals with obesity and with and without a prior history of AUD.
They compared patients who suffered from obesity who had T2DM (~33%) and those who did not (~67%); as well as patients with T2DM who suffered from obesity (~40%) and those who did not (~60%), and assessed whether there were potential interactions on the effects of semaglutide in patients with these two co-morbid conditions.
Outcomes
In total, 83,825 patients with obesity who had no prior diagnosis of AUD and were for the first time prescribed semaglutide (n=45,797) or non-GLP-1RA anti-obesity (naltrexone or topiramate, n=38,028), were included in the study. Compared to non-GLP-1RA anti-obesity medications, semaglutide was associated with a significantly lower risk of incident AUD diagnosis (0.37% vs 0.73%), consistent across gender, age group and race. Compared to naltrexone or topiramate, semaglutide was associated with a significantly lower risk of incident AUD diagnosis (0.35% vs 0.78%), consistent across gender, age group and race and in patients with and without T2DM.
There were 4,254 patients with obesity who had a prior diagnosis of AUD and were for the first time prescribed semaglutide (n=1470) or non-GLP-1RA anti-obesity (n=2784) medications. Again, compared to non-GLP-1RA anti-obesity medications, semaglutide was associated with a significantly lower risk of recurrent AUD diagnosis (22.6% vs 43.0%) and was consistent across gender, age group and race. Significant lower risks were observed in patients with T2DM and without T2DM. Compared to naltrexone or topiramate, semaglutide was associated with a significantly lower risk of incident AUD diagnosis (21.5% vs 59.9%), and was again consistent across gender, age group and race and in patients with and without T2DM.
“Our results find an association between reduced risk for incident and AUD relapse with the prescription of smaglutide in patients with obesity or T2DM,” the study authors concluded. “While these findings provide preliminary evidence of the potential benefit of semaglutide in AUD in real-world populations further randomised clinical trials are needed to support its use clinically for AUD.”
The findings were reported in the paper, ‘Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population’, published in Nature Communications. To access this paper, please click here
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