Early Fasting Serum Glucose or Weight Reduction With Tirzepatide and Metabolic Outcomes in People With Type 2 Diabetes: A Post Hoc Analysis of the SURPASS Trials

Objective To evaluate late (Week 40/42) metabolic outcomes by early glycemic response (<20% or ≥20% fasting serum glucose [FSG] reduction at Week 4) or weight response (<5% or ≥5% weight reduction at Week 8), respectively, in tirzepatide-treated participants with type 2 diabetes in the SURPASS trials. Research Design and Methods This post hoc analysis used pooled data across trials. Baseline characteristics, change from baseline to Week 40/42 for efficacy parameters, and gastrointestinal adverse events (GI AEs) were described and analyzed by early response in FSG (SURPASS-1 to -4; N=3,676) or weight (SURPASS-1 to -5; N=4,121) in the efficacy and safety analysis set, respectively. Results Early responders in FSG (50%) were younger, with higher glycemic parameters and lower weight at baseline. Early responders in weight (31%) had lower glycemic parameters and weight at baseline and a greater percentage were women and White. Early versus non-early responders in FSG or weight achieved better HbA1c (-2.6% versus -2.0% or -2.5% versus -2.2%) and weight (-11% versus -10% or -15% versus -8%) responses at Week 40/42 and greater improvements in blood pressure and lipids profile. Non-early responders also had clinically meaningful HbA1c and weight reductions with all tirzepatide doses. The incidence of GI AEs (generally mild-to-moderate events) decreased over time and was, in general, comparable between early and non-early responders. Conclusions Both early glucose and weight responses with tirzepatide were associated with better longer-term metabolic outcomes. Early response may be a good clinical indicator that could help inform treatment individualization to achieve therapeutic goals.