Dual GIP and GLP-1 receptor agonist tirzepatide improves beta-cell function and insulin sensitivity in type 2 diabetes

Context: Novel dual GIP and GLP-1 receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide.

Objective: Explore mechanisms of glucose control by tirzepatide.

Design: Post-hoc analyses of fasting biomarkers and multiple linear regression analysis.

Setting: 47 sites in 4 countries.

Patients or Other Participants: 316 subjects with Type 2 diabetes.

Interventions: Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), placebo.

Main Outcome Measures: Analyze biomarkers of beta-cell function and insulin resistance (IR) and evaluate WL contributions to IR improvements at 26 weeks.

Results: HOMA2-B significantly increased with dulaglutide and tirzepatide 5, 10, and 15 mg compared with placebo (p<0.02). Proinsulin/insulin  and proinsulin/C-peptide ratios significantly decreased with tirzepatide 10 and 15 mg compared with placebo and dulaglutide (p<0.007). Tirzepatide 10 and 15 ...