IMPORTANCE: 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.
OBJECTIVE: 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).
DESIGN, SETTING, AND PARTICIPANTS: 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.
EXPOSURES: Post-bariatric surgery treatment with an IBT (semaglutide, liraglutide, or tirzepatide) vs non-IBT AOMs (orlistat, phentermine, low-dose naltrexone, benzphetamine, phendimetrazine, or diethylpropion).
MAIN OUTCOMES AND MEASURES: 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.
RESULTS: 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.
CONCLUSIONS AND RELEVANCE: 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.
