In combination with renin-angiotensin system (RAS) inhibitors, use of either sodium-glucose cotransporter 2 (SGLT2) inhibitors or nonsteroidal mineralocorticoid receptor antagonists (MRA) reduces the risk for kidney and heart failure events in patients with diabetic kidney disease, investigators confirm. They pointed out that each drug class is associated with certain risks.

Given the lack of head-to-head comparisons among the drug classes, investigators performed a network meta-analysis of 17 randomized trials involving 22,981 patients. A subset had type 2 diabetes and stage 1-4 chronic kidney disease and were receiving angiotensin receptor blockers or angiotensin-converting enzyme inhibitors. The primary outcome was a composite kidney outcome of kidney failure, doubling of serum creatinine, or death from renal causes. Secondary outcomes included death from cardiovascular causes, nonfatal myocardial infarction or stroke, heart failure hospitalization, and all-cause mortality. The 4 safety outcomes were acute kidney injury (AKI), hyperkalemia, hyponatremia, and volume reduction.

Compared with no treatment or placebo, use of SGLT2 inhibitors in combination with RAS inhibitors was significantly associated with 38% decreased odds of the composite kidney outcome, Shuo Yang, MS, of the People’s Hospital of China Medical University, and colleagues reported in Diabetes, Obesity, and Metabolism. Use of the nonsteroidal MRA finerenone in combination with RAS inhibitors was significantly associated with 24% decreased odds of the composite outcome.

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The addition of SGLT2 inhibitors or nonsteroidal MRA significantly decreased the odds of heart failure hospitalization by 43% and 22%, respectively, compared with placebo. Use of SGLT2 inhibitors rather than nonsteroidal MRA was significantly associated with 27% decreased odds of heart failure hospitalization, the investigators reported. SGLT2 inhibitors also were significantly associated with 20% decreased odds of cardiovascular death and 21% decreased odds of all-cause mortality compared with placebo or no treatment.

Safety Outcomes

Treatment with a nonsteroidal MRA (eg, finerenone) or a non-selective aldosterone antagonist (eg, spironolactone) was significantly associated with 2.3- and 3.2-fold increased odds of hyperkalemia, respectively, compared with placebo or no treatment. These 2 drug classes were significantly associated with 2.7- and 3.9-fold increased odds of hyperkalemia, respectively, compared with SGLT2 inhibitors.

Non-steroidal MRA was significantly associated with 16.6- and 23.8-fold increased odds of hyponatremia compared with placebo and SGLT2 inhibitors, respectively.

Close monitoring of potassium and sodium levels is warranted in patients taking an MRA in combination with RAS blockade, according to Yang’s team.

SGLT2 inhibitors were significantly associated with 1.3-fold increased odds of volume reduction. These drugs should not be used in patients with unstable volumetric status or hypovolemia, Yang’s team noted.

The investigators found no increased risk of AKI. According to a SUCRA score analysis, SGLT2 inhibitors were the better choice to reduce the odds of AKI, hyperkalemia, and hyponatremia.


Yang S, Zhao L, Mi Y, He W. Effects of sodium-glucose cotransporter 2 inhibitors and aldosterone antagonists, in addition to renin-angiotensin system antagonists on major adverse kidney outcomes in patients with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab. Published online June 16, 2022. doi:10.1111/dom.14801