Cracking the Code—How the Individualized Metabolic Surgery Score Predicts Weight Loss with Tirzepatide in People with Type 2 Diabetes and Obesity

Introduction and Objective: People with type 2 diabetes (T2D) lose less weight in response to antiobesity medications compared to those without T2D. The individualized metabolic surgery score (IMSS), originally developed to predict T2D remission after bariatric surgery, inversely correlates with total body weight loss (TBWL) in response to semaglutide. IMSS reflects T2D severity, incorporating HbA1c, T2D medication use, insulin use, and T2D duration. This study aims to evaluate TBWL with tirzepatide across the IMSS severity spectrum and to identify specific IMSS parameters associated with lesser TBWL. Methods: This retrospective study included patients with T2D and obesity using tirzepatide for ≥12 months. Exclusion criteria were active malignancy, prior bariatric surgery or concurrent antiobesity medication use. We calculated IMSS at baseline. TBWL% at the last follow-up was stratified by IMSS quartiles (Q1-Q4). Data were analyzed using ANOVA, Tukey HSD, and univariable and multivariate regression, adjusting for age, sex and BMI. Results are reported as mean ± standard deviation. Results: We included 513 patients: 53% female, 95% White, 59 ± 11 years, BMI 38 ± 8 kg/m2. Male sex, older age, and lower BMI were associated with higher IMSS (p<0.001 for all). At 14 ± 1.4 months, TBWL% progressively decreased across IMSS quartiles: Q1, 14.2 ± 8 vs Q2, 11.2 ± 8 vs Q3, 10.9 ± 8 vs Q4, 9.7 ± 8; P<0.001. Pairwise analysis showed significant differences between Q2, Q3, and Q4 vs Q1. Notably, differences remained significant after adjusting for age, sex, and BMI. Longer T2D duration was the strongest predictor of poorer weight loss outcomes among all IMSS parameters: parameter estimate -0.1, 95% CI [-0.2, -0.01], p=0.04. Conclusion: Higher IMSS predicts lesser TBWL in patients with T2D and obesity treated with tirzepatide, with T2D duration being the strongest predictor of poorer outcomes. These findings provide valuable insights for patient counseling and setting realistic weight loss expectations. Disclosure: R. Castaneda: None. R. Rivera: None. D. Bechenati: None. J.L. Villamarin: None. M.A. Espinosa: None. E. Tama: None. J.L. Meek: None. M.D. Hurtado Andrade: Advisory Panel; Novo Nordisk. Research Support; Phenomix, National Institutes of Health. Funding: National Institute of Health (K12-AR084222)