Predictors of initial and sustained glycemic and weight response to tirzepatide: a post hoc analysis of SURPASS-4

TY - JOUR

T1 - Predictors of initial and sustained glycemic and weight response to tirzepatide

T2 - a post hoc analysis of SURPASS-4

AU - Pearson, Ewan

AU - Del Prato, Stefano

AU - Pavo, Imre

AU - Franco, Denise R.

AU - Zheng, Junyuan

AU - Nicolay, Claudia

AU - Hemmingway, Andrea

AU - Wiese, Russell J.

AU - Kahn, Steven E

N1 - © 2025 by the American Diabetes Association

PY - 2025/10

Y1 - 2025/10

N2 - This post hoc analysis assessed sustainability of lowered glycated hemoglobin (HbA 1c) and weight with tirzepatide in people with type 2 diabetes and increased cardiovascular risk. Participants achieving HbA 1c ≤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 HbA 1c ≤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 HbA 1c, higher HOMA of β-cell function (HOMA-B), metfor-min 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 HbA 1c, 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.

AB - This post hoc analysis assessed sustainability of lowered glycated hemoglobin (HbA 1c) and weight with tirzepatide in people with type 2 diabetes and increased cardiovascular risk. Participants achieving HbA 1c ≤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 HbA 1c ≤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 HbA 1c, higher HOMA of β-cell function (HOMA-B), metfor-min 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 HbA 1c, 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.

KW - Body weight reduction

KW - GIP and GLP-1 receptor agonist

KW - HbA1c reduction

KW - Predictors of reduction

KW - Predictors of sustainability

KW - Tirzepatide

KW - Type 2 diabetes

KW - Predictors of response

KW - Overweight/Obesity

KW - Prediction models

U2 - 10.2337/db25-0276

DO - 10.2337/db25-0276

M3 - Article

C2 - 40633089

SN - 0012-1797

VL - 74

SP - 1850

EP - 1862

JO - Diabetes

JF - Diabetes

IS - 10

M1 - db250276

ER -