Ertugliflozin as an add-on to standard treatment was shown to be non-inferior to placebo in terms of MACE (major adverse cardiac event) in this large-scale international study. This confirmed the cardiovascular safety of this modern antidiabetic drug. Given the excellent data to date from cardiovascular endpoint studies, expectations were very high.
At the Scientific Sessions of the American Diabetes Association (ADA) in June this year, the results of the phase III VERTIS-CV (“eValuation of ERTugliflozin effIcacy and Safety” cardiovascular) trial were announced [1]. Data from more than 8200 patients with type 2 diabetes and atherosclerotic cardiovascular disease in 531 centers in 34 countries were examined for the effects of ertugliflozin on a composite endpoint of cardiovascular mortality, nonfatal myocardial infarction, and stroke. The primary endpoint was defined as non-inferiority compared to placebo. VERTIS-CV is one of the studies ordered by the U.S. Food and Drug Administration (FDA) to demonstrate the cardiovascular safety of new antidiabetic drugs through clinical outcome studies. The previous cardiovascular end point studies EMPA-REG-OUTCOME (empagliflozin), CANVAS (canagliflozin), and DECLARE-TIMI-58 (dapagliflozin) each demonstrated a cardiopreventive effect of the SGLT inhibitors studied therein in addition to the safety evidence [2–4]. In particular, cardiovascular mortality and hospital admissions for heart failure were shown to be reduced. With the results in the DAPA-HF study, dapagliflozin has now been established as a new option for the treatment of heart failure patients, both in individuals with and without diabetes. Study evidence for renoprotective effects is also available for all three SGLT2 inhibitors mentioned.
Data from previous CVOTs induced high expectations
Given the remarkable study record of the aforementioned previous cardiovascular outcomes trials (CVOTs), the results of the VERTIS-CV study with ertugliflozin are almost a bit sobering. Although ertugliflozin (Steglatro®) [5] achieved a 30% reduction in the risk of hospitalization, other secondary endpoints of superiority of ertugliflozin over placebo were not met. These include time to first onset of cardiovascular death or hospitalization for heart failure, duration to cardiovascular-related death, and dialysis/transplantation or doubling of serum creatinine. Nevertheless, the outcomes of the VERTIS-CV trial are valuable as another contribution to the evidence-based assessment of the benefit-risk profile of SGLT-2 inhibitors in patients with type 2 diabetes. “The VERTIS-CV results add to the growing body of evidence regarding the clinical profile of ertugliflozin, including safety in patients with a history of cardiovascular disease,” summarized lead investigator Prof. Christopher P. Cannon, M.D., of Brigham and Women’s Hospital, Harvard Medical School, Boston. By showing that treatment with ertugliflozin did not increase the risk of a cardiovascular event compared with placebo, the overall study objective of demonstrating the cardiovascular safety of this SGLT inhibitor was achieved, Prof. Cannon said.
Literature:
- Cannon CP, et al: Results of the eValuation of ERTugliflozin EffIcacy and Safety CardioVascular Outcomes Trial (VERTIS CV). Presented at: 80th American Diabetes Association Scientific Sessions; June 16, 2020. symposium.
- Fitchett D, et al: EMPA-REG OUTCOME® Trial Investigators. Eur Heart J 2016; 37: 1526-1534.
- Mahaffey KW, et al: CANVAS Program Collaborative Group. Circulation 2018; 137: 323-334.
- Wiviott SD, et al: N Engl J Med 2019; 380: 347-357.
- Swiss Drug Compendium, www.compendium.ch
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