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 26 | |||
| Placebo (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) |
| Table. Changes from baseline in A1C, BW and SBP at Week 26 | |||
| Placebo (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) |
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..
