A Pooled Analysis of the Efficacy and Safety of Ertugliflozin as Add-On Therapy to Metformin

Abstract

Ertugliflozin (ERTU) is a highly selective sodium-glucose cotransporter 2 inhibitor in development for treatment of patients with type 2 diabetes mellitus (T2DM). This pooled analysis characterized the efficacy and safety of ERTU when used as add-on therapy to metformin (MET). Pooled data from 2 randomized, double-blind, placebo-controlled Phase 3 studies with similar design and patient population (NCT02033889 [VERTIS MET], NCT02036515 [VERTIS SITA2]) were analyzed. Adult patients with T2DM inadequately controlled on MET (± sitagliptin) with A1C ≥7.0 to ≤10.5% were randomized to placebo (PBO), ERTU 5 mg or 15 mg for 26 weeks. Mean baseline (BL) characteristics of patients (N=1083) were similar across pooled treatment groups (age 57.7 years; T2DM duration 8.6 years; A1C 8.1%; body weight [BW] 85.7 kg; systolic blood pressure [SBP] 130.6 mmHg; estimated glomerular filtration rate 89.4 mL/min/1.73 m2). Changes in A1C, BW and SBP after 26 weeks are shown in the Table. Relative to PBO, more patients receiving ERTU had A1C <7.0%, BW reduction of ≥5%, or SBP <130 mmHg (among patients with BL SBP ≥130 mmHg) at Week 26. ERTU had an overall similar safety profile to PBO, except for a higher incidence of adverse events (AEs) of genital mycotic infections and of AEs related to osmotic diuresis. Addition of ERTU to MET (± sitagliptin) provides reductions in A1C, BW and SBP, resulting in more patients achieving metabolic treatment goals.Table. Changes from baseline in A1C, BW and SBP at Week 26Placebo (n=362)Ertugliflozin 5 mg (n=363)Ertugliflozin 15 mg (n=358)Least squares mean change from baseline in A1C at Week 26 (95% CI), % Placebo-adjusted difference–0.1 (–0.2, 0.0) ––0.8 (–0.8, –0.7) –0.7 (–0.8, –0.6)–0.9 (–1.0, –0.8) –0.8 (–1.0, –0.7)Patients with A1C <7.0% at Week 26, n (%)59 (16.3)123 (33.9)143 (39.9)Least squares mean change from baseline in BW at Week 26 (95% CI), kg Placebo-adjusted difference–1.3 (–1.6, –1.0) ––3.2 (–3.4, –2.9) –1.8 (–2.3, –1.4)–3.0 (–3.3, –2.7) –1.7 (–2.1, –1.2)Patients with BW reduction ≥5% at Week 26, n (%)39 (10.8)115 (31.7)103 (28.8)Least squares mean change from baseline in SBP at Week 26 (95% CI), mmHg Placebo-adjusted difference–0.8 (–2.0, 0.5) ––4.1 (–5.3, –2.9) –3.4 (–5.1, –1.7)–4.9 (–6.1, –3.7) –4.1 (–5.8, –2.4)Patients with baseline SBP ≥130 mmHg (N) and with SBP <130 mmHg (n) at Week 26, n/N (%)32/171 (18.7)70/192 (36.5)71/189 (40.7) Disclosure R.A. Calle: Employee; Self; Pfizer Inc.. J. Liu: None. S. Huyck: Employee; Self; Merck & Co., Inc.. L. Wu: None. A. Pong: 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..