LAUSR

ABSTRACT Introduction Approximately 40% of people with type 2 diabetes (T2D) also have chronic kidney disease (CKD), which substantially increases their risk of cardiovascular (CV)-related complications and mortality. Until recently, no approved therapies have directly targeted inflammatory and fibrotic pathways that drive disease progression and organ damage in patients with CKD associated with T2D. Areas covered Finerenone is a potent, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) that targets fibrosis and inflammation by blocking overactivation of the MR in the kidneys and heart. Finerenone has been associated with significant reductions in kidney- and CV-related endpoints compared with placebo and minimal effects on serum potassium and kidney function in phase III trials involving >13,000 patients with diabetic kidney disease (DKD). In addition to reviewing the clinical data, this review compares the properties of finerenone with those of the older steroidal MRAs spironolactone and eplerenone. Expert opinion Unlike spironolactone and eplerenone, finerenone has demonstrated a favorable benefit-risk profile offering an effective new treatment for patients with CKD associated with T2D. Increases in serum potassium are predictable and manageable and should not discourage the use of finerenone in clinical practice. It is important to discuss where finerenone ‘fits best’ within the current DKD management landscape. Plain Language Summary Around 4 in 10 people with type 2 diabetes (T2D) also have a condition called chronic kidney disease (also frequently referred to as diabetic kidney disease). People with T2D and chronic kidney disease have an overactive protein called the mineralocorticoid receptor (MR for short) in their kidney and heart cells. Overactive MRs causes inflammation and cell injury and can eventually cause damage to people’s kidneys and heart. Mineralocorticoid receptor antagonists (MRAs for short) are a type of drug that can be used to block the activity of the MR to reduce inflammation and damage to the kidneys and heart. There are two types of MRA – steroidal MRAs and non-steroidal MRAs. Steroidal MRAs (spironolactone and eplerenone) are an older type of MRA. Finerenone is a non-steroidal MRA and is a newer type of MRA. Researchers studied the effects of finerenone in two clinical trials involving more than 13,000 people withchronic kidney disease and T2D. In these trials people who took finerenone had slower rates of kidney damage and less heart and heart-associated problems than people who took a dummy drug (called a placebo). Some people taking finerenone may have increased blood potassium levels (called hyperkalemia), but this side effect can be managed and so people can continue to take finerenone. Researchers are continuing to research and consider where finerenone “fits best” among the available treatment options for people with T2D and chronic kidney disease. Graphical abstract