Tirzepatide Treatment and Associated Changes in β-Cell Function and Insulin Sensitivity in People With Obesity or Overweight With Prediabetes or Normoglycemia: A Post Hoc Analysis From the SURMOUNT-1 Trial

OBJECTIVE We assessed insulin sensitivity and β-cell function in adults with obesity/overweight, without diabetes, treated with tirzepatide for 72 weeks. RESEARCH DESIGN AND METHODS This post hoc analysis from the Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1) trial investigated tirzepatide versus placebo in 2,539 participants with BMI ≥27 kg/m2 and either prediabetes or normoglycemia at baseline. Model-derived parameters of β-cell function and insulin sensitivity were assessed from oral glucose tolerance tests. RESULTS At week 72, tirzepatide treatment was associated with body weight reduction and improvements in insulin sensitivity and β-cell function measures overall and in participants with prediabetes or normoglycemia. In multivariate regression models, improvements in insulin sensitivity were associated mostly with weight reduction and partly with tirzepatide treatment, whereas enhancement in β-cell function was mostly associated with tirzepatide treatment. CONCLUSIONS In adults with obesity/overweight without type 2 diabetes, tirzepatide treatment was associated with improved β-cell function and insulin sensitivity, partly independent of weight reduction.