Predictors of Initial and Sustained Glycemic and Weight Response to Tirzepatide: A Post Hoc Analysis of SURPASS-4

This post hoc analysis assessed sustainability of lowered glycated hemoglobin (HbA1c) and weight with tirzepatide in people with type 2 diabetes and increased cardiovascular risk. Participants achieving HbA1c ≤48 mmol/mol (6.5%) or weight loss ≥10% at 52 weeks were evaluated for sustained glycemic or weight control and predictors of initial and sustained efficacy. For tirzepatide-treated participants achieving HbA1c ≤48 mmol/mol (6.5%) at 52 weeks, 75–84% sustained this until study end (median 81 weeks). Factors predicting achievement were higher tirzepatide dose, shorter diabetes duration, and lower HbA1c, higher HOMA of β-cell function (HOMA-B), metformin alone, and absence of albuminuria at baseline. Factors predicting sustained glycemic control were greater weight loss, smaller fasting glucose decrease, no sulfonylurea, and higher HOMA-B at 52 weeks. For participants achieving ≥10% weight loss at 52 weeks, 79–82% maintained weight loss. Factors predicting achievement were higher tirzepatide dose, female sex, no cardiovascular disease history, and lower baseline HbA1c, estimated glomerular filtration rate, and triglycerides. Greater decrease in LDL-cholesterol to 52 weeks predicted maintained weight loss. Greater weight loss and better β-cell function achieved with tirzepatide were the main predictors for sustained glycemic control in this post hoc analysis; no clinically meaningful predictor was identified for sustained weight control. Article Highlights We aimed to explore sustainability of lowered glycated hemoglobin (HbA1c) and weight with tirzepatide in a post hoc analysis. The question we wanted to answer was what predicted achieving and sustaining HbA1c and weight reduction in A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk (SURPASS-4). We found greater weight loss and improved β-cell function were the main predictors for sustained glycemic control with tirzepatide therapy. No clinically relevant predictor was identified for sustained weight loss. Simple clinical measures may predict initial and sustained glycemic control and initial weight loss with tirzepatide.