NEJM study confirms cardiac safety of Ertugliflozin in diabetes
Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, ertugliflozin was non-inferior to placebo concerning major adverse cardiovascular events, suggests a new trial whose findings have recently been published in The New England Journal Of Medicine.
Cardiovascular disease is the leading cause of illness and death in patients with type 2 diabetes.1-3 Type 2 diabetes is also a major risk factor for the development of heart failure and progression of renal disease.
Ertugliflozin is an oral, selective SGLT2 inhibitor that was approved by the Food and Drug Administration (FDA) in the United States and by regulatory authorities in other countries for the improvement of glycemic control in adults with type 2 diabetes.
The cardiovascular effects of ertugliflozin, an inhibitor of sodium-glucose cotransporter 2, have not been established.
The long-term effects of ertugliflozin on cardiovascular and renal outcomes were assessed in the Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial (VERTIS CV) by Christopher P. Cannon et. al. from the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School.
Researchers designed a multicenter, double-blind trial, where they randomly assigned patients with type 2 diabetes and atherosclerotic cardiovascular disease to receive 5 mg or 15 mg of ertugliflozin or placebo once daily.
With the data from the two ertugliflozin dose groups pooled for analysis, the primary objective was to show the noninferiority of ertugliflozin to placebo concerning the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke).
The first key secondary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure.
On data analysis, the following facts emerged.
- A total of 8246 patients underwent randomization and were followed for a mean of 3.5 years. Among 8238 patients who received at least one dose of ertugliflozin or placebo, a major adverse cardiovascular event occurred in 653 of 5493 patients (11.9%) in the ertugliflozin group and 327 of 2745 patients (11.9%) in the placebo group (hazard ratio, 0.97; 95.6% confidence interval [CI], 0.85 to 1.11; P<0.001 for noninferiority).
- Death from cardiovascular causes or hospitalization for heart failure occurred in 444 of 5499 patients (8.1%) in the ertugliflozin group and 250 of 2747 patients (9.1%) in the placebo group (hazard ratio, 0.88; 95.8% CI, 0.75 to 1.03; P=0.11 for superiority).
- The hazard ratio for death from cardiovascular causes was 0.92 (95.8% CI, 0.77 to 1.11), and the hazard ratio for death from renal causes, renal replacement therapy, or doubling of the serum creatinine level was 0.81 (95.8% CI, 0.63 to 1.04).
- Amputations were performed in 54 patients (2.0%) who received the 5-mg dose of ertugliflozin and in 57 patients (2.1%) who received the 15-mg dose, as compared with 45 patients (1.6%) who received placebo.
"The adverse events seen with ertugliflozin were consistent with the known risks of the medicines in the SGLT2 inhibitor class. As expected, genital mycotic infections occurred more frequently among women and men in either the ertugliflozin dose group than among those in the placebo group. The percentage of patients who underwent amputation was numerical — but not significantly — higher in either ertugliflozin dose group than in the placebo group, and the percentage of patients who had diabetic ketoacidosis was higher in either ertugliflozin dose group than in the placebo group (statistical testing was not performed)."Concluded the team.
For the full article click on the link: DOI: 10.1056/NEJMoa2004967
Primary source: The New England Journal Of Medicine