New VERTIS-CV Analysis Finds Renal Benefits for Ertugliflozin on Par With Other SGLT2s

Investigators for the VERTIS-CV trial last week presented data that show ertugliflozin offers renal protective benefits on par with those of rival sodium glucose cotransporter 2 (SGLT2) inhibitors, the drug class developed for diabetes now being studied to prevent heart and kidney failure.

Ertugliflozin (Steglatro, Merck) is a relative newcomer to the SGLT2 market, which is dominated by empagliflozin (Jardiance), dapagliflozin (Farxiga), and the first drug of the class, canagliflozin (Invokana).

Five years ago, a cardiovascular outcomes trial for empagliflozin shocked scientists when it showed a 38% reduction in cardiovascular mortality; while subsequent studies have shown other SGLT2 inhibitors offer benefits in heart and renal protection, that first result has never quite been matched. And in June, the VERTIS-CV trial fell short of showing superiority in its primary and secondary end points, despite a 30% drop in heart failure hospitalization.

On Wednesday during the European Association for the Study of Diabetes virtual meeting, David Z.I. Cherney, MD, PhD, of the University of Toronto, presented new evaluations of renal data from the study:

• A renal composite end point reported the primary outcome of renal death, dialysis or transplant, or doubling of serum creatinine. The end point was seen in 3.2% of the ertugliflozin group (5499 patients, taking doses of 5 mg or 15 mg). In the placebo group, the end point was seen in 3.9% of 2747 patients, for a hazard ratio (HR) of 0.81 (95.8%, CI 0.63-1.04, P = .08). Results favoring ertugliflozin were not significant.
• When investigators focused their analysis on an end point of a sustained 40% in the estimated glomerular filtration rate (eGFR), dialysis/transplant, or renal death; however, the difference was greater. The end point occurred in 2.05% of the ertugliflozin group vs 3.09% of the placebo groups, for a 34% reduction, driving largely by the smaller share of ertugliflozin patients seeing eGFR decline (HR 0.66; 95.0%, CI 0.50-0.88, P < .01).

This second evaluation is important because it matches the end point seen in the CANVAS trial for canagliflozin and the DECLARE-TIMI trial for dapagliflozin.

In addition, investigators found that the relative risk reduction for the kidney composite was similar across regardless of the patient’s stage of chronic kidney disease (CKD) or risk category, “demonstrating kidney benefits regardless of how CKD was defined.”

The study drug also significantly reduced urine albumin-to-creatinine ratio (UACR) in patients with a range of albuminuria levels, and seemed to offer the greatest benefit to those at highest risk of progressive diabetic kidney disease. Patients’ eGFR declined sharply at first, but were preserved over time.