Effects of sodium‐glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, and their combination on albuminuria in diabetic patients

Abstract

AbstractAimsDiabetes mellitus (DM) is the leading cause of chronic kidney disease. Albuminuria is associated with an increased risk of cardiovascular mortality. Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) and mineralocorticoid receptor antagonists (MRAs) protect against albuminuria; however, their combined effects on albuminuria are unclear. We performed a network meta‐analysis to investigate the effects of SGLT2‐Is, MRAs and their combination on albuminuria in type 2 DM.MethodsWe systematically searched PubMed, Medline, EMBASE and the Cochrane Library from inception up to 20 November 2022. We selected randomized control and crossover trials that compared MRAs, SGLT2‐Is, MRAs + SGLT2‐Is, or a placebo in patients with type 2 DM with a urinary albumin‐creatinine ratio (UACR) ≥30 mg/g creatinine. The primary outcome was the change in the UACR.ResultsThis meta‐analysis analysed 17 studies with 34 412 patients. The use of combination treatment with SGLT2‐Is and MRAs was associated with lower albuminuria compared with the use of SGLT2‐Is, MRAs, or the placebo alone [mean difference (95% CI): −34.19 (−27.30; −41.08), −32.25 (−24.53; −39.97) and −65.22 (−57.97; −72.47), respectively]. Treatment with SGLT2‐Is or MRAs alone caused a significant reduction in UACR compared with the placebo [mean difference (95% CI): −31.03 (−28.35; −33.72) and −32.97 (−29.68; −36.27), respectively]. The effects of MRAs on the UACR are comparable with those of SGLT2‐Is. Sensitivity analyses showed similar results.ConclusionCombination therapy with SGLT2‐Is and MRAs was associated with lower albuminuria in patients with type 2 DM compared with monotherapy with SGLT2‐Is or MRAs alone.