Efficacy and Safety of Ertugliflozin across Racial Groups in Patients with Type 2 Diabetes Mellitus (T2DM)

Abstract

Ertugliflozin (ERTU) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor for the treatment of T2DM. Pharmacokinetic analysis indicates ERTU plasma exposure is not affected by race. The efficacy and safety of ERTU by race was assessed in pooled analyses from 3 randomized, double-blind, placebo (PBO)-controlled, Phase 3 trials. Patients received ERTU 5 mg, 15 mg or PBO for 26 weeks. Least-squares (LS) means for change from baseline to Week 26 were calculated for hemoglobin A1C (A1C), body weight (BW) and systolic blood pressure (SBP). General and prespecified adverse events (AEs) were evaluated. The analysis included 1544 patients (white 73%; black 7%; asian 15%; other 5%). Baseline demographics and characteristics were generally similar across treatment groups and racial groups, except lower mean BW and BMI in Asians. No notable differences in A1C, BW and SBP reductions were observed across racial groups (Table 1), except for a greater SBP reduction observed in Blacks. Across racial groups there were no notable differences in general AEs with ERTU vs. PBO. An increase in genital mycotic infections was seen with ERTU vs. PBO across all racial groups. Precision of between-treatment effects was limited in Blacks, Asians and Others due to small group size. ERTU efficacy and safety was generally similar across racial groups although a greater reduction in SBP was observed in Blacks.Table 1. Least-squares Mean Change (Placebo-corrected) in A1C, Body Weight and SBP from Baseline to Week 26 by Racial Group (Excluding Rescue Approach)RaceErtugliflozin Dose (N)*δA1C (%) LS mean (95% CI)δBody Weight (kg) LS mean (95% CI)δSBP (mmHg) LS mean (95% CI)Overall5 mg (519)-0.8 (-0.9, -0.7)-1.8 (-2.2, -1.4)-3.4 (-4.8, -2.0)15 mg (510)-0.9 (-1.0, -0.8)-1.8 (-2.2, -1.4)-3.5 (-4.9, -2.0)White5 mg (382)-0.8 (-1.0, -0.7)-1.9 (-2.3, -1.4)-3.3 (-4.9, -1.6)15 mg (374)-1.0 (-1.1, -0.8)-1.7 (-2.2, -1.2)-3.5 (-5.1, -1.8)Black5 mg (34)-0.7 (-1.2, -0.2)-1.1 (-2.8, 0.6)-9.5 (-16.0, -2.9)15 mg (37)-0.8 (-1.3, -0.3)-2.2 (-3.9, -0.6)-8.1 (-14.6, -1.7)Asian5 mg ( 77)-0.8 (-1.1, -0.5)-1.9 (-2.6, -1.1)-1.8 (-5.3, 1.8)15 mg (77)-1.0 (-1.3, -0.8)-2.1 (-2.8, -1.4)-1.9 (-5.4, 1.7)Other5 mg (26)-0.3 (-0.9, 0.3)-1.7 (-3.2, -0.2)-3.5 (-11.3, 4.4)15 mg (22)-0.9 (-1.5, -0.3)-1.5 (-3.0, 0.1)-4.4 (-12.8, 3.9)CI, confidence interval; LS, Least Squares *N is the number of randomized patients who took at least one dose of study medication. The LS Means for Change from Baseline to Week 26 were estimated from a constrained longitudinal data analysis model. Disclosure J. Liu: None. L. Tarasenko: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc.. A. Pong: None. S. Huyck: Employee; Self; Merck & Co., Inc.. L. Wu: None. J.P. Mancuso: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc.. Employee; Spouse/Partner; Pfizer Inc.. Stock/Shareholder; Spouse/Partner; Pfizer Inc. S. Terra: Employee; Self; Pfizer Inc. B. Lauring: Employee; Self; Merck & Co., Inc..