New VERTIS-CV data: Kidney function preserved with ertugliflozin in type 2 diabetes
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New exploratory analyses show treatment with the SGLT2 inhibitor ertugliflozin reduced risk for worsening kidney function, dialysis or renal death among adults with type 2 diabetes compared with placebo.
In prespecified exploratory analyses presented at the virtual European Association for the Study of Diabetes annual meeting, researchers also reported the ertugliflozin (Steglatro, Merck) was associated with reduced urinary albumin to creatinine ratio in patients with albuminuria at baseline, including patients with microalbuminuria and macroalbuminuria who are at greatest risk for chronic kidney disease progression, as well as less decline in estimated glomerular filtration rate vs. placebo, suggesting preservation of kidney function over time.
“VERTIS-CV is yet another trial highlighting the benefits of the SGLT2 inhibitor class that supports the [American Diabetes Association] guidelines, and now it is on us as doctors to ‘get with the guidelines,’” Christopher P. Cannon, MD, a cardiologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, told Healio. “We need to follow the new guidance — to target this class of drugs by patient characteristics — notably, for those with atherosclerotic cardiovascular disease, heart failure and/or CKD, independent of glycemic control. It is a new paradigm, and an exciting one, on how we can use this class to bring important clinical benefits to patients in preventing heart disease events and decrease progression of kidney disease.”
As Healio previously reported, the initial findings from VERTIS-CV, presented at the American Diabetes Association Scientific Sessions in June and published this week in The New England Journal of Medicine, demonstrated that adults with type 2 diabetes and established atherosclerotic CVD were no more likely to experience a CV event during 3.5 years of follow-up with ertugliflozin compared with placebo.
In presenting findings from VERTIS-CV trial, a randomized controlled trial with more than 8,200 participants from 34 countries, researchers also said participants assigned to ertugliflozin saw a 30% reduction in risk for hospitalization for heart failure, a component of the composite secondary endpoint and a finding observed across all large CV outcomes studies with SGLT2 inhibitors completed to date. The HR for the original composite renal outcome of a doubling of serum creatinine from baseline, dialysis or transplant or renal death was 0.81, but the finding did not reach statistical significance (95% CI, 0.63-1.04).
“This was largely driven by a reduction in events of a doubling of serum creatinine,” David Cherney, MD, PhD, FRCPC, from the division of nephrology, department of medicine, University Health Network at the University of Toronto said during the presentation.
Cherney noted that definitions for renal-related composite outcomes varied across large CV outcomes trials for SGLT2 inhibitors, leading researchers with VERTIS-CV to assess kidney risk in different ways.
Compared with placebo, the HR for the exploratory renal composite outcome of sustained 40% decrease from baseline in eGFR, dialysis or kidney transplant or renal death was 0.66 (95% CI, 0.5-0.88).
“Of importance, when we looked at a sustained 40% reduction in eGFR, renal replacement therapy or renal death, there was a 34% reduction in this composite endpoint, which was statistically significant, of course using a lower bar in terms of the significant reduction in eGFR,” Cherney said.
Ertugliflozin was also associated with a 21% reduction in risk for progression to albuminuria compared with placebo (HR = 0.79; 95% CI, 0.72-0.86), Cherney said.
“The relative risk reduction for the kidney composite was similar across CKD stage, level of [urinary albumin to creatinine ratio] and KDIGO CKD risk category, demonstrating consistent kidney benefits regardless of how CKD was defined,” Cherney said. “We also saw significantly reduced [urinary albumin to creatinine ratio] in patients with a range of albuminuria at baseline, and preserved kidney function, especially in patients with macroalbuminuria at greatest risk of [diabetic kidney disease] progression.”
Cherney said the new renal analyses are currently under review for publication in a medical journal.
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Helena W. Rodbard, MD, FACP, MACE
VERTIS-CV is a cardiovascular outcomes trial designed to evaluate ertugliflozin, an SGLT2 inhibitor, in adults with type 2 diabetes and established CVD. The study confirmed the safety and noninferiority of ertugliflozin for the three-point major adverse CV events endpoint, but did not show any superiority. Similarly, no significant benefit of ertugliflozin was observed for the renal composite outcome, which consisted of death from renal causes, renal replacement therapy or doubling of serum creatinine levels. This contrasts with previous trials of SGLT2 inhibitors that have shown consistent reduction in the risks for both albuminuria and clinical renal composite outcomes.
It is unclear why the results in the VERTIS-CV did not reach significance, whereas significance was reached for many endpoints in studies with other drugs of the same class, with similar patient populations.
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Cherney D. VERTIS-CV Outcome. Presented at: EASD Annual Meeting; Sept. 21-25, 2020 (virtual meeting).
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