McNally, Allyson W

ABSTRACT Objective This study assessed the impact of sex and age on weight loss outcomes in patients receiving tirzepatide in real‐world clinical practice. Methods We conducted a retrospective cohort study of adults with overweight or obesity who initiated tirzepatide at Mayo Clinic between June 2022 and May 2024 and completed ≥ 12 months of continuous therapy. Primary outcome was total body weight loss percentage (TBWL%) at 15 months, stratified by sex and age groups (≤ 45, 46–59, ≥ 60 years). Results Among 1039 patients (57% women; mean age 56 ± 11 years), women achieved significantly greater TBWL% than men after 15 months of treatment (15.1% vs. 10.7%, p < 0.001). Patients aged ≤ 45 years had greater weight loss than those ≥ 60 years (15.1% vs. 12.3%, p = 0.024). In multivariable analyses, greater weight loss was independently associated with female sex, absence of type 2 diabetes, no prior obesity medication use, no concomitant weight gain‐promoting medications, and higher tirzepatide dosage. Age was not an independent predictor. Conclusions Sex, but not age, predicted weight loss with tirzepatide among individuals using the medication continuously for ≥ 12 months. These findings underscore the importance of incorporating sex‐specific considerations into personalized obesity treatment strategies.

Background/Objectives: Individuals with type 2 diabetes (T2D) achieve less total body weight loss (TBWL) with obesity medications compared to those without T2D. The individualized metabolic surgery (IMS) score, originally developed to predict T2D remission after bariatric surgery, inversely correlates with TBWL response to semaglutide. IMS reflects T2D severity, incorporating HbA1c and T2D duration and medication use. This study aims to evaluate TBWL with tirzepatide across IMS severity categories and identify predictors of response in a real-world cohort. Methods: This retrospective analysis included 717 adults with T2D using tirzepatide for overweight or obesity within the Mayo Clinic Health System. Patients were stratified by IMS severity (mild, moderate, severe) and quartiles. Primary endpoint: TBWL% at 15 months. Secondary endpoints: categorical thresholds (≥5%, ≥10%, ≥15%, ≥20%) and predictors of TBWL%. Linear mixed-effects models and regression models were employed. Results: At 15 months, TBWL was greater in mild versus severe IMS groups (14.8% vs. 11.0%, p = 0.015), with similar trends across quartiles. The proportion achieving ≥ 20% TBWL was nearly two-fold higher in mild versus severe IMS (27% vs. 14%, p = 0.03). Female sex independently predicted greater TBWL, whereas insulin use, higher T2D medication burden (particularly weight-promoting agents), and HbA1c > 7% were associated with less TBWL. Conclusions: Tirzepatide produced clinically meaningful TBWL across all IMS categories, although TBWL declined with increasing IMS severity. Glycemic control and T2D medication use emerged as strong predictors of TBWL. The IMS score may serve as a practical tool to anticipate weight-loss trajectories, guide personalized treatment decisions, and inform patient counseling.