KDIGO provided recommendations on SGLT2 inhibitors and nonsteroidal MRAs in patients with diabetes and CKD

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and nonsteroidal mineralocorticoid receptor antagonists (MRAs) are now recommended for more patients with chronic kidney disease (CKD), but data are needed on their cost-effectiveness, an ACP Journal Club commentary said.

A consensus statement on caring for patients with diabetes and chronic kidney disease (CKD) from Kidney Disease: Improving Global Outcomes (KDIGO) included 13 recommendations and 52 practice points for clinicians. It recommended a layered approach to care, starting with a foundation of lifestyle interventions, self-management, and first-line pharmacotherapy (such as sodium-glucose cotransporter-2 [SGLT2] inhibitors) followed by additional drugs such as glucagon-like peptide-1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists (MRAs).

The guideline synopsis was published by Annals of Internal Medicine online Jan. 10 and in the March print issue. The KDIGO guidance was summarized in the October 2022 ACP Diabetes Monthly. The following commentary by Matthew van Norman, DO, and Donald A. Molony, MD, ACP Member, was published in the ACP Journal Club section of Annals of Internal Medicine on May 2.

The KDIGO guidelines have been updated to reflect new data on the benefits of SGLT2 inhibitors and nonsteroidal MRAs in patients with type 2 diabetes and CKD. They recommended SGLT2 inhibitors in more patients with CKD, including those with estimated glomerular filtration rates (eGFRs) as low as 20 mL/min/1.73 m2. Nonsteroidal MRAs were also recommended for patients with type 2 diabetes, eGFR ≥25 mL/min/1.73 m2, and at least moderately increased albuminuria.

Newer meta-analyses that included CKD-focused trials of SGLT2 inhibitors show kidney and cardiovascular (CV) benefits. SGLT2 inhibitors had a trend toward decreased benefit in more advanced CKD (eGFR of 30 to 45 mL/min/1.73 m2), but better renal outcomes were still maintained. Clinical trials are needed to determine whether these agents will benefit patients with eGFR <20 mL/min/1.73 m2. In the 2 new trials of nonsteroidal MRAs evaluated for the guideline, finerenone showed CV benefits in patients with CKD and type 2 diabetes with varying levels of albuminuria, although only FIDELIO-DKD found decreased CKD progression. Patients who were receiving dialysis or had kidney transplantation were excluded from the SGLT2 inhibitor and nonsteroidal MRA trials. Further research is needed to determine whether patients with eGFR <20 mL/min/1.73 m2 should continue these drugs as they reach advanced kidney failure or need for kidney replacement therapy.

SGLT2 inhibitors and nonsteroidal MRAs should improve quality of life due to renal and CV benefits from decreased CKD progression. Goal-directed therapy including these drugs may be cost-effective because the need for renal replacement therapy may be delayed. Until such cost-effectiveness evaluations have been completed, the new KDIGO recommendations may not be achievable for some patients and health systems. However, the guidelines emphasize the benefits of early and broad application of these agents in managing patients with type 2 diabetes and proteinuric CKD.