Tirzepatide as Monotherapy Improved Markers of Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes (SURPASS-1)

Abstract

Context: Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for treatment of type 2 diabetes (T2D). SURPASS-1, a phase 3 trial of tirzepatide monotherapy in people with early T2D, enables evaluating effects of tirzepatide on pancreatic beta-cell function and insulin sensitivity (IS) without other background antihyperglycemic medications. Objective: Explore changes in biomarkers of beta-cell function and IS with tirzepatide monotherapy. Design: Post hoc analyses of fasting biomarkers with analysis of variance and mixed model repeated measures. Setting: Forty-seven sites in 4 countries. Patients: Four hundred seventy-eight T2D participants. Intervention: Tirzepatide (5, 10, 15 mg), placebo. Main Outcome Measure(s): Analyze biomarkers of beta-cell function and IS at 40 weeks. Results: At 40 weeks, markers of beta-cell function improved with tirzepatide monotherapy vs placebo with reductions from baseline in fasting proinsulin levels (49-55% vs -0.6%) and in intact proinsulin/C-peptide ratios (47-49% vs -0.1%) (P