JCEM model ties tirzepatide's glucose edge to hepatic glucose suppression

The wire

1. 01Researchers built a longitudinal systems model from a 28-week trial comparing tirzepatide 15 mg with semaglutide 1 mg in type 2 diabetes, integrating fasting glucose, insulin, insulin sensitivity and HOMA-B.
2. 02Tirzepatide's superior fasting glucose control was driven primarily by greater insulin-independent suppression of hepatic glucose production, suggesting a target beyond beta-cell stimulation or added weight loss.
3. 03This is model-based secondary analysis, not a new trial; simulations of enhanced weight loss sped early glycemic improvement but did not lower long-term fasting glucose.

From the source

Quantitative Insights into Tirzepatide and Semaglutide Using Longitudinal Systems Modeling

The Journal of clinical endocrinology and metabolism · 2026 Sep 21 · Yang B, Cabrera O, Mather KJ et al.