Clinical-genetic Predisposition and Medium-Term Outcomes after Bariatric Surgery: A 5-Year Validation of the OBEGEN Score

Background:Weight-loss outcomes after bariatric surgery (BS) show interindividual variability that is not fully explained by clinical factors. In the OBEGEN study we previously developed a clinical-genetic score combining three clinical variables with nine single nucleotide polymorphisms to predict weight-loss success at 12-18 months after BS. In the present study we evaluated the usefulness of this clinical-genetic score to predict longitudinal weight-loss trajectories up to five years after BS. Methods:Multicenter retrospective cohort study including 342 adults who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (2018-2020) with available genetic data. Patients were classified as into higher or lower predicted response groups using the OBEGEN cut-off (0.662). The primary outcome was percentage total weight loss (%TWL) assessed from 6 months to 5 years. Longitudinal trajectories were analyzed using linear mixed-effects models adjusted for baseline BMI, sex, type 2 diabetes, and center. Secondary outcomes included the proportion achieving >20% TWL and recurrent weight gain. Results:Patients in the higher predicted response group achieved greater %TWL throughout follow-up than those in the lower predicted response group (adjusted β = 2.60%, p = 0.009). Differences emerged early after surgery and remained stable over time without progressive divergence. At 5 years, a higher proportion of patients in the higher predicted response group maintained >20% TWL (78.7% vs. 60.0%, p = 0.001). Discriminatory performance of response to BS was moderate but consistent (area under the receiver operating characteristic curve 0.674 at 1 year; 0.608 at 5 years). Conclusion:The OBEGEN clinical-genetic score stratifies patients into distinct medium-term weight-loss trajectories after bariatric surgery, supporting its utility as a preoperative tool for risk stratification and personalized management in obesity.