Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: the VERTIS SITA2 placebo-controlled randomized study

5 years ago

Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: the VERTIS SITA2 placebo-controlled randomized study

Gregory Golm, Guillermo Amorin, Jie Liu, Samuel S. Engel, Darcy Hille, Roy Eldor, Jeremy Johnson, Yuqin Liao, Brett Lauring, Steven G. Terra, Susan Huyck, James P. Mancuso, Samuel Dagogo-Jack

Aims To assess ertugliflozin in patients with type 2 diabetes inadequately controlled on metformin and sitagliptin. Materials and Methods In this double-blind randomized study (NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0–10.5% [53–91 mmol/mol] on metformin ≥1500 mg/day and sitagliptin 100 mg/day; estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2) were randomized to ertugliflozin 5 mg once-daily, 15 mg once-daily, or placebo. Primary efficacy endpoint was change from baseline in HbA1c at Week 26; treatment was continued until Week 52. Results 464 patients were randomized (mean baseline HbA1c 8.0% [64.3 mmol/mol]; eGFR 87.9 mL/min/1.73 m2). After 26 weeks, placebo-adjusted least squares (LS) mean changes in HbA1c from baseline were –0.7% (–7.5 mmol/mol) and –0.8% (–8.3 mmol/mol) for ertugliflozin 5 mg and 15 mg, respectively (both p<0.001); 17.0%, 32.1% and 39.9% of patients receiving placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively, had HbA1c <7.0% (53 mmol/mol). Significant reductions in fasting plasma glucose, body weight (BW) and systolic blood pressure (SBP) were observed with ertugliflozin relative to placebo. The positive effects of ertugliflozin on glycaemic control, BW, and SBP were maintained through Week 52. A higher incidence of genital mycotic infections was observed in male and female patients receiving ertugliflozin (3.7–14.1%) versus placebo (0–1.9%) through Week 52. The incidence of urinary tract infections, symptomatic hypoglycaemia and hypovolaemia adverse events were not meaningfully different across groups. Conclusions Ertugliflozin added to metformin and sitagliptin was well-tolerated, and provided clinically meaningful, durable glycaemic control, BW and SBP reductions versus placebo over 52 weeks. Trial registration number: Clinicaltrials.gov NCT02036515

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/dom.13116