Benefit of Finerenone on CV, Kidney Outcomes Not Modified by GLP-1 RA Use

Article

A greater reduction in UACR was observed with finerenone in patients taking GLP-1RA at baseline.

Peter Rossing, MD

Peter Rossing, MD

New findings suggest the observed benefit of finerenone on composite cardiovascular and kidney outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are not modified by glucagon-like peptide-1 receptor agonist (GLP-1 RA) use.

The study investigators saw an increased effect observed for urine albumin-to-creatinine ratio (UACR), noting that it may suggest a different mechanism of reduction in albuminuria.

“A greater reduction in UACR was observed with finerenone in patients taking GLP-1RA at baseline,” wrote study author Peter Rossing, MD, Steno Diabetes Center Copenhagen. “Incidence of hyperkalemia was similarly increased with finerenone irrespective of GLP-1RA use at baseline.”

These findings were presented at the 2022 American Diabetes Association Annual Meeting in New Orleans, Louisiana.

In both the FIDELIO-DKD and FIGARO-DKD studies, the agent reduced the risk of cardiorenal outcomes in patients with CKD and T2D. Data from FIDELIO-DKD found the effects of finerenone on kidney and cardiovascular outcomes were consistent irrespective of GLP-1 RA use. However, the analyses were shown to be better powered to evaluate change in UACR.

Thus, investigators extended the analyses to patients in both studies to incorporate a larger population with broader-specified inclusion criteria.

Individuals with T2D and CKD (UACR ≥30 - <300 mg/g and eGFR ≥25 - ≤90 mL/min/1.73 m2 or UACR ≥300-≤5000 mg/g and eGFR ≥25 mL/min/1.73 m2) treated with optimized renin-angiotensin system blockade were randomized to finerenone or placebo.

Then, investigators analyzed the effects of finerenone on cardiovascular (death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (kidney failure, sustained ≥57% eGFR decline, or renal death) composite outcomes and on UACR at month 4 by GLP-1 RA use.

From a total of 13,026 patients, 944 (7.2%) received GLP-1 RAs at baseline. The findings were consistent irrespective of GLP-1 RA use at baseline for the cardiovascular composite outcome (hazard ratio [HR], 0.76; 95% CI, 0.52 - 1.11 with GLP-1 RA; HR, 0.87, 95% CI, 0.79 - 0.96 without GLP-1 RA; P for interaction, 0.63).

The results were additionally consistent irrespective of GLP-1 RA use at baseline for the kidney composite outcome (HR, 0.82; 95% CI, 0.45 - 1.48 with GLP-1 RA; HR, 0.77, 95% CI, 0.67 - 0.89 without GLP-1 RA; P for interaction, 0.79).

Further, investigators saw a greater reduction in UACR with finerenone in patients taking GLP-1 RA at baseline (placebo-corrected change -38% with GLP-1 RA and -31% without GLP-1 RA use; P for interaction, 0.03).
Rossing noted that the incidence of hyperkalemia was found similarly increased with finerenone regardless of GLP-1 RA use at baseline.

The study, “Finerenone in Patients Across the Spectrum of CKD and T2D By GLP-1 RA Use,” was presented at ADA 2022.

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