The following is a summary of “Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2),” published in the July 2024 issue of Endocrinology by Frias, et al.

In previous SURPASS studies, tirzepatide demonstrated superior efficacy in reducing hemoglobin A1c (HbA1c) and body weight compared to other treatments. It also showed improved markers of insulin sensitivity and β-cell function. For a post hoc analysis, researchers sought to explore changes in biomarkers of β-cell function and insulin sensitivity, as well as to compare the efficacy profiles of tirzepatide and semaglutide across different baseline biomarker quartiles.

The study was a post hoc analysis of the SURPASS-2 phase 3 trial, in which participants were randomly assigned to receive either weekly subcutaneous tirzepatide (5, 10, or 15 mg) or semaglutide 1 mg for 40 weeks. The analysis was conducted across 128 sites in 8 countries. A total of 1,879 participants with type 2 diabetes were included in the study. Participants received once-weekly subcutaneous injections of either tirzepatide (5 mg, 10 mg, or 15 mg) or semaglutide 1 mg. The primary outcomes measured included changes in homeostatic model assessment indices for pancreatic β-cell function (HOMA2-B) and insulin resistance (HOMA2-IR), as well as changes in fasting glucagon, fasting C-peptide, and fasting insulin levels.

At week 40, tirzepatide (5 mg, 10 mg, 15 mg) showed a greater increase in HOMA2-B compared to semaglutide 1 mg, with increases of 96.9% to 120.4% for tirzepatide versus 84.0% for semaglutide (P < .05). All doses of tirzepatide also resulted in a greater reduction in HOMA2-IR (15.5% to 24.0%) compared to semaglutide 1 mg (5.1%) (P < .05). Tirzepatide 10 mg and 15 mg led to significant reductions in both fasting C-peptide (5.2% to 6.0%) and fasting glucagon (53.0% to 55.3%), whereas semaglutide 1 mg resulted in an increase in C-peptide (3.3%) and a reduction in glucagon (47.7%) (P < .05). Additionally, reductions in HbA1c and body weight were greater with all tirzepatide doses compared to semaglutide within each HOMA2-B and HOMA2-IR baseline quartile.

The post hoc analysis revealed that tirzepatide provided consistent and significantly greater improvements in HbA1c and body weight compared to semaglutide, irrespective of baseline β-cell function and insulin resistance levels.

Reference: academic.oup.com/jcem/article/109/7/1745/7585180