Incretin-based therapies, alcohol and tobacco use, and acute substance-related events: emerging implications for cardiovascular medicine.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual incretin agonists are now familiar drugs in obesity, diabetes, heart failure, and cardiovascular prevention. At the same time, a clinically relevant but molecule-specific human literature suggests that selected incretin-based therapies, particularly semaglutide for alcohol-related outcomes, may also modify alcohol use, tobacco use, and selected acute substance-related events. Alcohol currently has the strongest signal. Small randomized studies suggest semaglutide can reduce laboratory alcohol self-administration and craving, whereas an earlier exenatide trial was neutral overall but suggested benefit in participants with obesity. Large registry and EHR studies further associate GLP-1RA exposure with lower alcohol-related hospitalization, lower incident or recurrent alcohol use disorder, and lower alcohol-related event rates. Tobacco evidence is more limited but now includes a pilot smoking-cessation trial with exenatide and a target-trial emulation linking semaglutide with fewer tobacco use disorder-related healthcare encounters. Evidence beyond alcohol and tobacco, and tirzepatide specific evidence, remains preliminary, although lower rates of opioid overdose, alcohol intoxication, and cannabis use disorder have been reported in observational analyses. For cardiologists, the key question is not whether incretin therapies should be viewed as addiction drugs, but whether established cardiometabolic therapies may also modify cardiovascular relevant risk behaviors.