Dr George Bakris Compares FIDELIO-DKD Renal Outcomes With Those of SGLT2 Inhibitor Trials

Although their underlying mechanisms differ, finerenone reduces albuminuria to the same extent as SGLT2 inhibitors, said George Bakris, MD, professor of medicine and director of the American Heart Association Comprehensive Hypertension Center at the University of Chicago Medicine.

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Can you elaborate on how FIDELIO-DKD findings on finerenone compare to those shown in trials of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes?

So let's be very clear. First we have to define finerenone before we can really talk about comparisons. Finerenone is distinctly different, not only from the SGLT2 inhibitors, but distinctly different from its cousins spironolactone and eplerenone. Spironolactone and eplerenone are steroidal mineralocorticoid receptor blockers. Finerenone is a non-steroidal mineralocorticoid receptor blocker, which means its chemistry is very different, pharmacokinetics are very different, and frankly, its clinical properties and effects are very different. Finerenone does not lower blood pressure, not significantly, 1 millimeter. Finerenone does not affect glucose. So in that way, it's very different than the spironolactone, eplerenone, and for that matter, SGLT-2s.

Finerenone, however, is very anti-inflammatory and there's a lot of basic science data on that. It's unclear whether SGLT2s are dramatically anti-inflammatory, although there is some evidence for that. So, SGLT2s have been found in multiple outcome trials to have both cardio and renal benefits. The mechanisms of action go way beyond glucose lowering, or blood pressure lowering. We fully do not understand how SGLT2s work to benefit both the heart and the kidney. Finerenone, which by the way, is not on the market yet. Finerenone reduces albuminuria to the same extent as SGLT2s, gave a benefit in slowing progression of kidney disease, not quite as good as the SGLT2s but similar, and in that sense, did not have any impact on blood glucose, or blood pressure. So one of the differences is SGLT2s did have a blood pressure lowering effect of about 3 and a half millimeters. It wasn't statistically significant, but 3 and a half millimeters is something. Finerenone had a 1.5 millimeter reduction in blood pressure, clearly not significant by any stretch of the imagination, and yet had a similar benefit. So its mechanism of benefit is clearly different than SGLT2s. While there may be some overlap, we don't know just yet. The other thing is in FIDELIO-DKD, about 5% of the patients, 5% of 5700, were on an SGLT2. Unfortunately, the numbers are too small when you look at the events to make a statement about whether there was additivity or synergy between the 2 compounds.