Novel SGLT2 inhibitor improves glycemic control in T2DM
Two Phase 3 studies (VERTIS MET and VERTIS SITA) of ertugliflozin, an investigational oral SGLT2 inhibitor in development to help improve glycemic control in adults with type 2 diabetes, met their primary endpoints. In the studies, both doses of ertugliflozin tested (5 mg and 15 mg daily) achieved statistically significant reductions in HbA1c over a two- to three-month timeframe, when added to metformin or in initial co-administration with sitagliptin. The results of these studies, along with 52-week extension data from three other studies in the VERTIS clinical development program of ertugliflozin, were presented at the 77th Scientific Sessions of the American Diabetes Association (ADA) in San Diego.
VERTIS MET, a 26-week study, evaluated the efficacy and safety of ertugliflozin in combination with metformin, compared with placebo and metformin, in adults with type 2 diabetes uncontrolled on metformin monotherapy. The study showed patients taking ertugliflozin 5 mg or 15 mg and metformin experienced greater reductions in HbA1c compared to placebo (0.7 percent and 0.9 percent, respectively, compared with 0.0 percent for placebo, p<0.001, for both comparisons). Ertugliflozin in combination with metformin also met a secondary endpoint in the study, as significantly more patients taking either ertugliflozin 5 mg or 15 mg achieved the ADA’s recommended HbA1c treatment goal of less than 7.0 percent compared with placebo and metformin. As add-on therapy to metformin, treatment with ertugliflozin also resulted in significant reductions in fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP), compared with placebo.
The 26-week VERTIS SITA study compared the efficacy and safety of initial combination therapy with ertugliflozin and the DPP-4 inhibitor sitagliptin with placebo. In this study, patients taking ertugliflozin 5 mg or 15 mg, in combination with sitagliptin 100 mg, experienced greater reductions in HbA1c compared with patients taking placebo alone (1.6 percent and 1.7 percent, respectively, compared with 0.4 percent in patients taking placebo, p<0.001 for both comparisons). Additionally, the co-administration of ertugliflozin and sitagliptin met a secondary endpoint in the study, as significantly more patients taking ertugliflozin 5 mg or 15 mg, in combination with sitagliptin 100 mg, achieved the HbA1c treatment goal of less than 7.0 percent. Treatment with the initial combination of ertugliflozin and sitagliptin also resulted in significant reductions in FPG, body weight and SBP, compared with placebo.
Adverse events reported were largely in line with events reported with other SGLT-2 inhibitors, including genital mycotic infection, which was higher among females compared with placebo.
Ertugliflozin is being investigated in the VERTIS clinical development program, which is comprised of nine Phase 3 trials in approximately 12,600 adults with type 2 diabetes. VERTIS CV, the ongoing cardiovascular (CV) outcomes trial of ertugliflozin, recently completed enrollment with approximately 8,000 patients. The primary endpoint of VERTIS CV is to assess the non-inferiority of ertugliflozin to placebo on the composite of CV death, nonfatal myocardial infarction or nonfatal stroke (MACE). In 2016, the trial was expanded and pre-specified secondary endpoints were added to test for superiority on the composite of CV death and hospitalization for heart failure, and for superiority on CV death alone.
Marketing applications for ertugliflozin and for two fixed-dose combination products (ertugliflozin and sitagliptin; ertugliflozin and metformin) are under review with the U.S. Food & Drug Administration (FDA) and the European Medicines Agency.