Insulin resistance does not affect finerenone efficacy for lowering CV, kidney risks
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Key takeaways:
- Finerenone is associated with lowering CV risk and delaying CKD progression for adults with type 2 diabetes.
- The drug’s efficacy is similar for adults with insulin resistance and those who are insulin sensitive.
Adults with type 2 diabetes and chronic kidney disease derive similar cardiovascular and kidney benefits from finerenone, regardless of their level of insulin resistance, according to findings published in Diabetes Care.
As Healio previously reported, finerenone (Kerendia, Bayer), a nonsteroidal mineralocorticoid receptor antagonist, was associated with reduced CV event risk as well as delayed progression of CKD for adults with type 2 diabetes and CKD in a pair of phase 3 trials. In a post hoc analysis of those trials, researchers said the observed risk reduction for CV and kidney outcomes was not affected by baseline insulin resistance as measured by estimated glucose disposal rate (eGDR).
“Finerenone provided consistent CV and kidney protection in patients with CKD and type 2 diabetes, irrespective of baseline insulin resistance,” Thomas Ebert, MD, endocrinologist and clinical scientist at medical department III – endocrinology, nephrology and rheumatology at University of Leipzig Medical Center in Germany, and colleagues wrote. “However, patients with insulin resistance were at greater risk of CV events compared with those without [insulin resistance]. This aligns with previous studies, supporting the hypothesis that eGDR is an important predictor of CVD.”
Researchers collected data from the phase 3 FIDELIO-DKD and FIGARO-DKD trials. FIDELIO-DKD examined kidney failure and CKD progression for adults with type 2 diabetes and CKD, whereas FIGARO-DKD assessed CV mortality and morbidity among adults with type 2 diabetes and CKD. Both trials randomly assigned participants, 1:1, to once-daily oral finerenone at titrated doses of 10 mg or 20 mg, or matching placebo. The CV outcome was a composite of CV death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure. The kidney composite outcome was kidney failure, a sustained decrease in estimated glomerular filtration rate of 57% or more for at least 4 weeks or renal death. Researchers measured eGDR to assess insulin resistance. Adults were considered to have insulin resistance if they had an eGDR less than the study population’s median of 4.1 mg/kg/min, Those with an eGDR of more than 4.1 mg/kg/min were considered insulin sensitive.
There were 13,026 adults included in the analysis, of whom 6,484 had insulin resistance with an eGDR of less than 4.1 mg/kg/min. The median follow-up was 3 years.
In FIGARO-DKD, adults who received finerenone had a lower risk for CV events than those receiving placebo (HR = 0.86; 95% CI, 0.78-0.95). In the full study group, increased eGDR from baseline to follow-up was associated with a lower risk for the CV composite outcome, regardless of treatment group (HR = 0.88; 95% CI, 0.86-0.91; P < .0001). Adults who were insulin resistant had a higher incidence rate of CV events than adults who were not insulin resistant, both in the finerenone and placebo groups. There was no difference in finerenone’s reduction of CV risk based on baseline eGDR.
In FIDELIO-DKD, adults receiving finerenone had a lower risk for kidney outcomes compared with those receiving placebo (HR = 0.77; 95% CI, 0.67-0.88; P = .0002). The risk for kidney outcomes was similar for adults with insulin resistance compared with those without insulin resistance in the full study group, regardless of treatment. Baseline insulin resistance did not affect the risk for kidney events for adults receiving finerenone. Finerenone was associated with a reduction in urine albumin-to-creatinine ratio and a slowing of eGFR decline, regardless of insulin resistance.
“This finding provides indirect support to the growing body of evidence that insulin resistance is not significantly associated with the development of CKD-related outcomes,” the researchers wrote.
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