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

by sugaradmin



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.





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