Incretin-Based Therapies and Post-Bariatric Surgery Alcohol Use Disorder.

Abstract

Patients who have undergone bariatric surgery have an elevated risk for alcohol use disorder (AUD). Incretin-based therapies (IBTs) may be associated with reward pathways in addition to weight loss. To evaluate whether IBT after bariatric surgery is associated with a lower risk of new-onset AUD and initiation of medications for AUD (MAUDs) compared with non-IBT antiobesity medications (AOMs). This retrospective cohort study included 15 382 adults who underwent bariatric surgery and subsequently received an AOM between January 1, 2020, and January 1, 2024, with outcomes assessed up to 2 years after AOM initiation. Data were derived from a multi-institutional US electronic health record network. Propensity score matching (1:1) balanced baseline covariates. Data were analyzed September 14, 2025. Post-bariatric surgery treatment with an IBT (semaglutide, liraglutide, or tirzepatide) vs non-IBT AOMs (orlistat, phentermine, low-dose naltrexone, benzphetamine, phendimetrazine, or diethylpropion). Outcomes of interest were incidence rates (per 1000 person-years) and hazard ratios (HRs) of new-onset AUD and initiation of MAUDs, estimated using Kaplan-Meier and Cox proportional hazards regression models. The study included 15 382 patients who underwent bariatric surgery and subsequently received AOMs (11 194 IBT [mean (SD) age, 51.4 (11.6) years; 8855 women (79.1%)]; and 4188 non-IBT [mean (SD) age, 45.1 (11.0) years; 3587 women (86.6%)]). After propensity score matching, 3990 patients were included in each group. Use of IBT was associated with a lower incidence of AUD (2.4 vs 5.2 per 1000 person-years) and a lower hazard of developing AUD (HR, 0.45; 95% CI, 0.25-0.81; P = .006) vs non-IBT use. Use of IBT was also associated with a lower incidence of initiating MAUDs (15.2 vs 25.6 per 1000 person-years) and a lower hazard of MAUD initiation (HR, 0.59; 95% CI, 0.46-0.75; P < .001). Results were consistent across sensitivity analyses, including restriction to AOM initiation within 5 years of bariatric surgery and requiring 3 or more AOM prescriptions. In this cohort study of patients who underwent bariatric surgery, IBT was associated with a 55% lower risk of new-onset AUD and a 41% lower risk of initiation of MAUDs compared with non-IBT AOMs. These findings suggest potential neurobehavioral benefits associated with IBTs that may inform AOM selection in this high-risk population. Prospective studies are warranted to confirm these associations and examine long-term liver-related outcomes.