Mineralocorticoid Receptor Antagonist Combined with SGLT2 Inhibitor versus SGLT2 Inhibitor Alone in Chronic Kidney Disease: A Meta-Analysis of Randomized Trials

Abstract

Introduction: Sodium glucose co-transporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRAs) reduce the progression of kidney disease. Whether the combination of these agents provides additional benefits compared to SGLT2i alone is worth exploring using data from randomized trials designed for this purpose. The aim of the study was to assess the randomized treatment effect of MRAs combined with SGLT2i versus SGLT2i alone on markers of kidney and cardiovascular health.

Methods: Random-effects meta-analysis of randomized trials testing the combination of MRAs with SGLT2i versus SGLT2i alone on albuminuria, blood pressure, estimated glomerular filtration rate (eGFR), and serum potassium among patients with chronic kidney disease (CKD).

Results: Four randomized trials were included with a total of 272 patients with CKD: eGFR varying between 30 and 60 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) between 90 and 500 mg/g, with >60% having type 2 diabetes. Treatment with MRAs plus SGLT2i versus SGLT2i alone reduced UACR by -33.6% (-42.6 to -24.7%), p < 0.001, I2 = 0%. MRAs plus SGLT2i versus SGLT2i alone reduced systolic blood pressure by -6.1 mm Hg (-8.9 to -3.3) mm Hg, eGFR by -3.4 mm Hg (-5.2 to -1.6) mm Hg, and increased serum potassium by + 0.23 mmol/L (0.15-0.34) mmol/L; p < 0.001 for all, without significant heterogeneity between trials (I2 <25%).

Conclusion: In this meta-analysis, MRAs plus SGLT2i provided greater reductions in albuminuria and blood pressure compared to SGLT2i alone. Larger randomized trials with longer follow-up should test whether MRA/SGLT2i combination therapies improve cardiovascular and renal outcomes compared to SGLT2i alone.

Keywords: Aldosterone synthase inhibitors; Mineralocorticoid receptor antagonists; Sodium glucose co-transporter 2 inhibitors; Therapy combination.