VERTIS-CV: Ertugliflozin CV neutral, HF benefit seen in type 2 diabetes
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Adults with type 2 diabetes and established atherosclerotic cardiovascular disease were no more likely to experience a CV event during 3.5 years of follow-up with the SGLT2 inhibitor ertugliflozin compared with placebo, study data show.
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 (Steglatro, Merck) 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.
“In patients with type 2 diabetes and prevalent atherosclerotic CVD, ertugliflozin, when added to guideline-directed secondary preventive therapies, was noninferior vs. placebo for the [major adverse CV events] endpoint,” Christopher P. Cannon, MD, senior physician at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, said during a presentation at the virtual American Diabetes Association Scientific Sessions. “The key secondary composite endpoint of CV death or hospitalization for heart failure did not differ significantly by group, nor did CV death, but a 30% lower risk for hospitalization for was observed with ertugliflozin. Looking at the overall pattern of the effect on these endpoints, in particular hospitalization for and renal outcomes, we find that these are really in line with those [results] seen in other large trials.”
Cannon and colleagues analyzed data from 8,246 adults with type 2 diabetes and atherosclerotic CVD assigned once-daily ertugliflozin 5 mg (n = 2,752), once-daily ertugliflozin 15 mg (n = 2,747) or daily placebo (n = 2,747). Mean age of participants was 64 years, with 70% men and 88% of participants white. Mean duration of type 2 diabetes was 13 years; mean HbA1c was 8.2% and mean estimated glomerular filtration rate was 75 mL/min/1.73m2; however, about 22% of participants had an eGFR of 60 mL/min/1.73m2 or less.
CV findings
Overall, the primary outcome of major adverse CV events was reported in 653 participants assigned ertugliflozin (5 mg and 15 mg doses) and 327 participants assigned placebo (11.9% for both) for an HR of 0.97 (95% CI, 0.85-1.11), Cannon said. The key secondary endpoints of superiority for ertugliflozin placebo were not met. HR for time to first occurrence of the composite of CV death or hospitalization for HF was 0.88 (95% CI, 0.75-1.03).
“While we hypothesized that we would have shown more significant preventive cardiovascular benefits, the overall pattern of benefit is consistent with what has been seen with other drugs in this class,” Canon said in a press release announcing the findings.
The prespecified endpoint of hospitalization for HF, while not a part of the hierarchicaltesting sequence, showed a 30% reduction in the risk of hospitalization for ertugliflozin vs. placebo (2.5% vs. 3.6%; HR=0.7; 95% CI, 0.54-0.9).
Renal trends
Although other CV outcomes trials have shown renal benefits with SGLT2 inhibitors, VERTIS-CV only showed a trend in the initial renal analysis, 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. The trial showed an effect on kidney-related outcomes, such as effects on acute and chronic eGFR over time, which is generally consistent with other SGLT2 inhibitor trials. The HR for the composite outcome of renal death, dialysis, transplantation or a doubling of serum creatinine was 0.81 for ertugliflozin vs. placebo (95% CI, 0.63-1.04), which did not reach significance, he said.
“Importantly, the definitions of renal-related composite outcomes did vary across the trials,” Cherney said. “Further work from VERTIS-CV analyzing these other ways of assessing kidney risk over time are ongoing.”
The safety profile of ertugliflozin was consistent with findings reported in previous SGLT2 inhibitor studies, according to researchers.
In summarizing the overall findings, Cherney said VERTIS-CV provides further evidence of the CV safety of SGLT2 inhibitors for the treatment of individuals with type 2 diabetes, and adds to the evidence of benefit for hospitalization that has been consistent across the class.
“Meta-analyses support contemporary society recommendations to prioritize the use of SGLT2 inhibitors, independent of glucose control considerations, in patients with type 2 diabetes with, or at high risk for, CV and renal complications,” Cherney said.
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Cannon C, et al. Results of the evaluation of ertugliflozin efficacy and safety cardiovascular outcomes trial (VERTIS-CV). Presented at: American Diabetes Association Scientific Sessions; June 12-16, 2020 (virtual meeting).
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