Safety Trial OF ERTUGLIFLOZIN Expanded for CV Outcomes

Reported by: John G. Ryan, Dr.P.H., University of Miami Miller School of Medicine

Highlights: 1. VERTIS Mono compared ertugliflozin 5 mg and 15 mg daily to placebo 2. VERTIS Factorial compared combination of ertugliflozin + sitagliptin to sitagliptin alone 3. Both studies met primary outcomes of greater reductions in glycosylated hemoglobin (HbA1c) 4. VERTIS CV is a third trial that was recently expanded to include composite measures of cardiovascular (CV) outcomes in type 2 diabetes patients

The results of two Phase 3 studies of the SGLT-2 inhibitor ertugliflozin were announced at the 76th Scientific Sessions of the American Diabetes Association, held in New Orleans, LA, from June 10-14, 2016.

VERTIS Mono compared ertugliflozin, a sodium glucose cotransporter (SGLT)- 2 inhibitor, as monotherapy with placebo. Patients randomized to ertugliflozin 5 mg and 15 mg had significantly greater Hba1c reductions of .99% and 1.16% respectively, compared with placebo (p<0.001).

VERTIS Factorial examined the impact of co-administration of ertugliflozin and the DPP-4 sitagliptin. Investigators announced that this study also met its primary endpoint, with greater reductions in HbA1c observed in patients taking ertugliflozin in combination with sitagliptin compared to either of the oral medications alone. Patients in the combination group experienced an HbA1c reduction of 1.5% compared to the group using ertugliflozin 5 mg alone (1.0%), ertugliflozin 15 mg alone (1.1%) and sitigliptin 100 mg alone (1.1%; p<0.001 for both combinations vs individual treatments).

VERTIS CV represents a third trial in the VERTIS family of nine trials. VERTIS CV was expanded to test for superiority in improving CV outcomes in type 2 diabetes patients. With the expansion and revised protocol, the trial will enroll approximately 8,000 patients with type 2 diabetes and established vascular disease. New secondary endpoints were added to the protocol to determine superiority on the composite outcome of CV death and hospitalization for heart failure and superiority on CV death alone. The primary outcome of VERTIS CV continues to be the non-inferiority of ertugliflozin vs placebo on the MACE composite of CV death, non-fatal myocardial infarction and nonfatal stroke.

The VERTIS clinical program includes nine Phase 3 trials in approximately 12,600 adults with type 2 diabetes. The manufacturers of ertugliflozin and sitagliptin plan to submit New Drug Applications to the US Food and Drug Adminsitration for ertugliflozin and two fixed-dose combinations of ertugliflozin plus sitagliptin and ertugliflozin plus metformin.