Discussion
Gastrointestinal symptoms, substance abuse
OBESE, DISORDERS
The main finding of the present study is that participants treated for smoking cessation drink significantly less alcohol after 12 weeks of treatment with dulaglutide compared with placebo, without correlation to smoking status. Our results thus support the hypothesized effect of GLP-1 agonists on alcohol intake in humans.The role of GLP-1 in reward-related processes has been demonstrated in preclinical studies. GLP-1 receptors are present in the mesolimbic reward system (The population of the present study was predominantly obese (BMI > 29.9 kg/mParticipants in our study received standard smoking cessation therapy, i.e., behavioral counselling and varenicline. Behavioral counselling is a form of psychotherapy implemented in treatment of SUD, including AUD. Varenicline has been found to reduce alcohol intake, especially in smokers, but also independently of smoking status (In pursuit of alternative reinforcers, patients quitting smoking may increase their consumption of alcohol (Gastrointestinal symptoms are common side effects of GLP-1 agonists (Smoking and drinking are closely associated (In analogy to the effects on alcohol-mediated reward, in preclinical studies, GLP-1 agonism has been found to also attenuate reward induced by other substances, i.e., psychostimulants (The present study has limitations. First, our participants did not per se suffer from AUD or SUD and the subgroup of heavy drinkers was too small to provide valuable results. Whether our findings can be extended to heavy- or binge-drinking smokers or nonsmoking AUD patients, and how smoking status influences the effect of GLP-1 agonists on alcohol intake needs to be investigated. Second, our primary endpoint of alcohol consumption is self-reported and therefore subjective. However, we were not able to assess objective measurements to quantify alcohol intake, such as biomarkers, in the present study. Furthermore, we did not assess drinking patterns, such as percent heavy-drinking days, abstinence, time spent drinking, or the context in which our participants drank. Third, in our study, participants received dulaglutide for only 12 weeks. Preclinical data show that alcohol intake was reduced for 3 weeks after discontinuation of dulaglutide in male but not female rats (In conclusion, our analysis showed an effect of a GLP-1 agonist on alcohol intake in humans and our results thus strengthen the rationale for implementing GLP-1 agonists in pharmacological AUD treatment. However, it has to be considered that AUD is characterized by a wide range of drinking behaviors and prevalent comorbid psychiatric disorders, including substance abuse. Thus, treatment strategies need to be multidimensional and personalized, taking into account psychosocial components. To identify the GLP-1 agonist’s role in the treatment of AUD and SUD, further studies are needed, elucidating which patients would benefit and whether GLP-1 agonists improve long-term abstinence.