Use of GLP‐1 receptor agonists and subsequent risk of alcohol‐related events. A nationwide register‐based cohort and self‐controlled case series study

Abstract

Animal studies have related glucagon-like peptide 1 receptor agonists (GLP-1) to lower alcohol intake. We examined whether GLP-1 was associated with risk of alcohol-related events in a nationwide cohort study and a self-controlled case series analysis including all new users of GLP1 (n = 38 454) and dipeptidyl peptidase 4 inhibitors (DPP4) (n = 49 222) in Denmark 2009-2017. They were followed for hospital contacts with alcohol use disorder or purchase of drugs for treatment of alcohol dependence in nationwide registers from 2009 to 2018. Associations were examined using Cox proportional hazard and conditional Poisson regression. During follow-up of median 4.1 years, 649 (0.7%) of participants were registered with an alcohol-related event. Initiation of GLP-1 treatment was associated with lower risk of an alcohol-related event (Hazard ratio = 0.46 (95%CI: 0.24-0.86) compared with initiation of DPP4 during the first 3 months of follow-up. Self-controlled analysis showed the highest risk of alcohol-related events in the 3-month pretreatment period (incidence rate ratio [IRR] = 1.25 (1.00-1.58)), whereas the risk was lowest in the first 3-month treatment period (IRR = 0.74 (0.56-0.97). In conclusion, compared with DPP4 users, individuals who start treatment with GLP-1 had lower incidence of alcohol-related events both in cohort and self-controlled analyses.

Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population

“…These beneficial effects are consistent with anecdotal reports that patients prescribed semaglutide describe reduced desire to drink alcohol while on the medication 9 and with recent clinical reports; one documenting reduced alcohol drinking with semaglutide or tirzepatide based on analyses of social media texts and follow up of selected participants 10 , and another of decreased symptoms of AUD in a case series of patients treated with semaglutide 11 . It is also consistent with a small clinical trial study of the GLP-1RA drug exenatide, which significantly reduced heavy drinking days and total alcohol intake in patients with obesity 12 and with a register-based study in Demark showing that GLP-1RAs (though semaglutide was not included) compared with dipeptidyl peptidase 4 inhibitors (DPP4) were associated with lower incidence of alcohol-related events in 2009–2017 13 . It is also consistent with preclinical studies that documented reduced drinking in rodents exposed to semaglutide 8 and that prevented relapse in a rat model of alcohol dependence 7 .…”

The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission

“…However, exploratory analyses showed that exenatide significantly reduced alcohol drinking in a subgroup of patients with AUD and comorbid obesity (BMI > 30 kg/m 2 ) ( 113 ). Further highlighting a potential role for GLP-1 analogues in AUD management, a recent cohort study, complemented with a self-controlled case series analysis, suggested that the use of GLP-1 analogues (grouped as a class and prescribed for their currently approved indications) might be associated with lower incidence of alcohol-related events ( 114 ).…”

A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder

“…The study included 38,454 new users of GLP-1 agonists and 49,222 users of dipeptidyl peptidase 4 inhibitors (DPP4). The findings revealed that initiating GLP-1 treatment was linked to a significantly lower risk of alcohol-related events compared to initiating DPP4 treatment during the first three months of follow-up [ 103 ].…”