Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET)

Introduction We evaluated efficacy and safety of ertugliflozin, an SGLT2 inhibitor, in type 2 diabetes mellitus (T2DM) inadequately controlled (HbA1c, 7.0–10.5%) on metformin monotherapy (≥1500 mg/day for ≥8 weeks). Methods Double-blind, 26-week, multicentre study with ongoing 78-week extension; 621 participants randomized 1:1:1 to placebo, ertugliflozin 5 or 15 mg/day. Primary endpoint: change from baseline in HbA1c at week 26. Secondary efficacy endpoints: change from baseline at week 26 in fasting plasma glucose (FPG), body weight, systolic/diastolic blood pressure (SBP/DBP); participants with HbA1c <7.0% (53 mmol/mol). Pre-specified adverse events (AEs) of special interest and percent change from baseline in bone mineral density (BMD) were also assessed at week 26. Results At week 26, the placebo-adjusted least-squares mean change from baseline HbA1c (8.1%) was −0.7% and −0.9% for ertugliflozin 5 and 15 mg, respectively (both P < 0.001), to final means of 7.3% and 7.2%, respectively. The odds of HbA1c <7.0% were significantly greater in both ertugliflozin groups vs placebo. Ertugliflozin significantly reduced FPG, body weight, SBP and DBP vs placebo. Incidence of genital mycotic infections was increased in ertugliflozin groups (females: placebo, 0.9%; ertugliflozin 5 mg, 5.5%; 15 mg, 6.3% [P = 0.032]; males: 0; 3.1%; 3.2%), as was incidence of urinary tract infections and symptomatic hypoglycaemia. Incidence of hypovolaemia AEs was similar across groups. Ertugliflozin had no adverse impact on BMD at week 26. Conclusions Ertugliflozin added to metformin in inadequately controlled T2DM improved glycaemic control, reduced body weight and BP, but increased genital mycotic infections. ClinicalTrials.gov identifier: NCT02033889.