Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study

What is it about?

Plain language summary In the FIDELIO-DKD study, treatment with the drug finerenone improved outcomes in the kidney and cardiovascular systems when tested against placebo in patients with chronic kidney disease and diabetes. The current study explored these same outcomes in two subgroups of patients based on characteristics at the start of finerenone or placebo treatment. In the first analysis, patients were compared based on their blood sugar (glucose) control (higher or lower blood sugar levels). In the second analysis, patients were compared based on whether they were or were not receiving insulin treatment. Finerenone treatment reduced the risk of having a kidney or cardiovascular event (such as starting dialysis or having a heart attack) than placebo regardless of the patient’s use of insulin or blood sugar status at the start of treatment. The occurrence of side effects with finerenone was similar regardless of insulin use or blood sugar level at the start of treatment. Overall, the study shows that finerenone can provide kidney and cardiovascular benefits to patients with chronic kidney disease and diabetes, irrespective of their blood sugar levels when they start treatment with finerenone and whether or not they are treated with insulin. Chronic kidney disease (CKD) in patients with type 2 diabetes is a major global health challenge, affecting an estimated 160 million people aged 20–79 years worldwide (1-3). Clinical guidelines for the management of CKD in patients with type 2 diabetes recommend control of hypertension and hyperglycemia, with individualized targets for the level of HbA1c of <6.5% (48 mmol/mol) to <8% (64 mmol/mol), as well as the use of a renin–angiotensin system blocker (an ACE inhibitor or angiotensin receptor blocker [ARB]) and, more recently, a sodium–glucose cotransporter-2 inhibitor (SGLT-2i) (4-7). Insulin is often used as a glucose-lowering agent in patients with CKD and type 2 diabetes, especially in patients with moderate-to-severe CKD where many other glucose-lowering agents cannot be used (8). It has been suggested that insulin treatment may increase sodium retention and hypertension (9), and hyperinsulinemia has been associated with inflammation in patients with type 2 diabetes (10). Insulin is often used when beta-cell failure is apparent and oral agents have failed; thus, insulin use at baseline may be suggestive of patients with complicated diabetes (11). Available evidence suggests that glycemic control influences kidney risk in patients with type 2 diabetes. Observational data suggest that poor glycemic control increases the risk for progression of CKD in patients with type 2 diabetes with moderately elevated albuminuria (12), and data from clinical trials have shown that intensive blood glucose control improves kidney outcomes in patient groups with type 2 diabetes and type 2 diabetes with mild CKD (13-15). However, evidence from large phase III trials regarding the relationship between glycemic control and disease outcomes in patients with moderate-to-severe CKD and type 2 diabetes is lacking. The prognostic implication and response to mineralocorticoid receptor antagonist (MRA) treatment relative to glycemic control as reflected by HbA1c levels is not well understood (16). Limited available data suggest that spironolactone may increase HbA1c levels in patients with and without diabetes, whereas the more selective steroidal MRA eplerenone has no effect on HbA1c levels (17,18). Finerenone is a novel, selective, nonsteroidal MRA that significantly reduced the risk of adverse kidney and cardiovascular (CV) outcomes in patients with CKD and type 2 diabetes in the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease; NCT02540993) phase III trial, without influencing HbA1c levels (19,20). The main aim of this analysis was to evaluate kidney, CV, and safety outcomes from the FIDELIO-DKD trial according to baseline HbA1c level, and to determine whether baseline glycemic control affects the previously reported benefits of treatment with finerenone. Furthermore, the effects of insulin treatment at baseline on efficacy and safety outcomes were investigated, because of the interdependency of insulin treatment and glycemic control (serum HbA1c levels) in patients with CKD and type 2 diabetes.

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