Finerenone confers consistent cardiorenal benefits in patients with CKD and T2D regardless of SGLT-2i use
17 Nov 2021
byAudrey Abella
In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) who were receiving the novel nonsteroidal MRA* finerenone, use of SGLT-2is** at baseline did not influence treatment outcomes, according to a subgroup analysis of the FIDELITY*** trial presented at ASN 2021.
“Despite SGLT-2i treatment being recommended for patients with CKD and T2D, further options are needed,” said Professor Peter Rossing from the University of Copenhagen, Denmark, during his virtual presentation.
In two separate trials, canagliflozin and dapagliflozin reduced the risk of kidney disease progression on top of RAS# inhibition in patients with CKD with or without T2D. [N Engl J Med 2019;380:2295-2306; N Engl J Med 2020;383:1436-1446] “However, residual risks remained. [Therefore,] SGLT-2i treatment is probably not sufficient alone,” Rossing pointed out. “We need to do more for our patients than RAS and SGLT-2 inhibition. Maybe combining SGLT-2is and finerenone is a way to go.”
Preclinical data reflect the benefit of an SGLT-2i-finerenone combination. Reductions in the incidences of cardiac fibrosis and survival were seen with either empagliflozin or finerenone monotherapy, more so with a combination of the two agents. [Am J Nephrol 2021;52:642-652]
Rossing and colleagues conducted a pooled analysis using patient data sets from the FIDELIO-DKD and FIGARO-DKD trials. The combined cohort comprised >13,000 patients with T2D and CKD who were on optimized RAS inhibitor therapy. Of these, 877 were on an SGLT-2i. Participants were randomized to receive either finerenone or placebo. [ASN 2021, abstract SA-OR22]
Compared with placebo, finerenone led to reductions in the cardiovascular (CV) composite endpoint## regardless of SGLT-2i use (adjusted hazard ratios [adjHRs], 0.63 and 0.87 [with and without SGLT-2is, respectively]; pinteraction=0.41). The effect was similar for HHF## (adjHRs, 0.45 and 0.80; pinteraction=0.16).
Similarly, renal benefit was consistent regardless of baseline SGLT-2i use. Reductions in the kidney composite endpoint## were seen with finerenone vs placebo among those who were (adjHR, 0.42) and were not on SGLT-2is (adjHR, 0.80; pinteraction=0.29). The 40-percent eGFR### reduction from baseline was also achieved with finerenone regardless whether patients were on SGLT-2is (adjHR, 0.70) or not (adjHR, 0.84; pinteraction=0.59).
“[The] p values for interaction [in both CV and kidney outcomes] were not significant, indicating that the benefit of finerenone is similar whether or not patients are treated with an SGLT-2i,” explained Rossing.
Finerenone also conferred reductions in UACR###, both among those who were (–37 percent) and were not on SGLT-2is (–32 percent). “[These imply that] finerenone improved albuminuria in patients with T2D and CKD irrespective of SGLT-2i use at baseline. Reduction in albuminuria is a surrogate endpoint, which is associated with a lower risk of kidney disease progression or low risk for CV events or mortality,” said Rossing.
Safety outcomes with finerenone also remained consistent irrespective of SGLT-2i use. There were no major differences in rates of adverse events (AEs) leading to treatment discontinuation (4.1 percent [SGLT-2i] vs 6.5 percent [no SGLT-2i]) or serious AEs leading to discontinuation (1.6 percent vs 2.3 percent). For hyperkalaemia leading to discontinuation, the rates were lower with vs without SGLT-2is (1.1 percent vs 1.7 percent). “[Nonetheless,] we need more data to substantiate this,” said Rossing.
“Further studies are required to clarify any additional clinical benefits with combined finerenone and SGLT-2i therapies in this patient population,” Rossing concluded.