The effects of ertugliflozin on β‐cell function: Pooled analysis from four phase 3 randomized controlled studies

AIMS To identify potential predictors and mediators of changes in β-cell function in response to ertugliflozin treatment in people with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS Data from patients with T2DM randomized to ertugliflozin (5 or 15 mg; observations from both doses were pooled) or placebo in four phase 3 clinical studies (clinicaltrials.gov: NCT01958671, NCT02226003, NCT02036515, NCT02099110) were pooled and analyzed. Change from baseline in β-cell function at Week 26 was assessed and its potential predictors and mediators were analyzed by linear and multiple regression analyses. RESULTS Compared with placebo, ertugliflozin improved β-cell function when assessed by the mean percent change from baseline (95% CI) in homeostatic model assessment (HOMA)-%β (ertugliflozin: 14.7% [12.3, 17.1]; placebo: -0.4% [-3.4, 2.5]) but not when assessed by change in the C-peptide index following a mixed meal tolerance test. Change in HOMA-%β correlated with change from baseline in HbA1c, treatment with ertugliflozin, and weakly with change from baseline in body weight. In the ertugliflozin group, change in HOMA-%β correlated with baseline fasting plasma glucose (FPG; r=0.235; P<0.001), baseline HbA1c (r=0.138; P<0.001), baseline HOMA of insulin resistance (HOMA-IR; r=0.162; P<0.01), and baseline HOMA-%β (r=-0.321, P<0.001) in linear regression analyses. Multiple regression analyses yielded similar results. CONCLUSION In people with T2DM, ertugliflozin treatment improves fasting β-cell function but no effect on postprandial β-cell function was observed in this analysis. Improvement in HOMA-%β was predicted by high baseline FPG, HbA1C, HOMA-IR, and low baseline HOMA-%β, and mediated by ertugliflozin treatment, and improved HbA1c and body weight. This article is protected by copyright. All rights reserved.