Since the arrival of GLP-1 analogues (aGLP-1) in the therapeutic armamentarium for type 2 diabetes (T2D) and obesity, other therapeutic and protective effects of this class of molecules are regularly reported. Thus, if studies have highlighted their cardio, neuro and nephroprotective properties, others point to their potential effectiveness in alcohol and tobacco use disorders, and substances more generally. Thus, a research letter published in the Jama Network Open reported the results of a cohort study showing a reduction in alcohol consumption among individuals taking anti-obesity medications, including aGLP-1.
“aGLP-1s, whose receptors are expressed in brain regions thought to be involved in reward and addiction, have been shown to reduce symptoms of substance use and dependence disorders in preclinical studies” , explain the authors of a literature review on the subject published in Drug and Alcohol Dependence, concluding that aGLP-1 could be “a possible new therapeutic option in addiction”. A mechanism of action is also pointed out in studies focusing on weight loss enabled by aGLP-1.
Anti-obesity drugs would lead to a reduction in alcohol consumption
The authors of the recent research letter show that aGLP-1 may be associated with a lower incidence of alcohol use disorders, using data from individuals participating in a weight control program and having started treatment with anti-obesity drugs (AOD) (metformin, bupropion, naltrexone, first and second generation aGLP-1). In this cohort (n = 14,053 individuals), 86.2% took a second generation aGLP-1 (tirzepatide, semaglutide) and more than half (53.3%) reported consuming alcohol.
During follow-up, almost a quarter (24.2%) of participants reduced their alcohol consumption, more markedly when body mass index was high and consumption was heavy. The authors think thus “that there could be properties of MAO that lead to reduction” of consumption, they evoke “a reduction in cravings” for naltrexone and “an attenuation of the reward effects of alcohol as for food” with aGLP-1. For participants on metformin, a reduction was also observed and the authors linked it to participating in a weight loss program.
Focus on aGLP-1 and substance use disorders
Published a little earlier in mid-November in Jama Psychiatry, another study, from Sweden, looked at aGLP-1 (liragultide, semaglutide) in alcohol use disorders (AUD). The objective was to find out if the risk of hospitalization for AUD decreased with taking aGLP-1 for the same individual, compared to periods when they did not take it. Included were 227,866 individuals with AUD, including 6,276 taking aGLP-1, with a median follow-up of 8.8 years. In total, with 58.5% of patients hospitalized for AUD in total, the authors found a lower risk of being admitted if taking semaglutide (HR = 0.64) or liraglutide (HR = 0.72) . In addition, this risk was also lowered for other substance use disorders.
In tobacco use disorder this time, an emulated essay published this summer in Annals of Internal Medicine shows that T2DM patients taking semaglutide, compared to those treated with other anti-diabetics, had a significantly lower risk of tobacco use disorder, and lower rates of prescription and consultation for smoking cessation. These results are observed for patients with or without obesity.
Finally, another study published in Nature reports a benefit of semaglutide in cannabis use disorder, in patients with obesity or type 2 diabetes. Furthermore, a few months later, the same team published in Nature communications real-life data showing a beneficial effect of semaglutide on the incidence and recurrence of alcohol use disorders.
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