Reduction in the magnitude of serum potassium elevation in combination therapy with esaxerenone (CS-3150) and sodium-glucose cotransporter 2 inhibitor in patients with diabetic kidney disease: Subanalysis of two phase III studies.

Abstract

AIMS/INTRODUCTION:

We evaluated the effect of co-administration of esaxerenone and a sodium-glucose cotransporter 2 (SGLT2) inhibitor on the magnitude of serum potassium elevation in Japanese patients with diabetic kidney disease.

MATERIALS AND METHODS:

We carried out a prespecified subanalysis of data from two phase III studies: a multicenter, randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes and microalbuminuria (J308); and a multicenter, single-arm, open-label trial in patients with type 2 diabetes and macroalbuminuria (J309). Changes in serum potassium levels during the studies and other measures were evaluated according to SGLT2 inhibitor use.

RESULTS:

In both studies, time-course changes in serum potassium levels, and incidence rates of serum potassium elevation were lower in patients with co-administration of SGLT2 inhibitor in both the placebo and esaxerenone groups than those without the inhibitor. In contrast, time-course changes and mean percentage changes from baseline in urinary albumin-to-creatinine ratio, the proportion of patients with albuminuria remission and time-course changes in blood pressure did not change with or without SGLT2 inhibitor, whereas the albumin-to-creatinine ratio and blood pressure were reduced with esaxerenone. The blood glucose-lowering effect of SGLT2 inhibitor was not affected by esaxerenone.

CONCLUSIONS:

In Japanese patients with type 2 diabetes and albuminuria treated with esaxerenone, concomitant use of SGLT2 inhibitor reduced the magnitude of serum potassium elevation without any change of its antihypertensive and albuminuria-suppressing effects. Co-administration of esaxerenone and SGLT2 inhibitor might be a beneficial treatment option for patients with diabetic kidney disease.

• Authors: Kenichi Shikata, Sadayoshi Ito, Naoki Kashihara, Masaomi Nangaku, Takashi Wada, Yasuyuki Okuda, Tomoko Sawanobori, Kotaro Sugimoto
• Journal: Journal of diabetes investigation (J Diabetes Investig) Vol. 13 Issue 7 Pg. 1190-1202 (Jul 2022) ISSN: 2040-1124 [Electronic] Japan
• PMID: 35199478 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Chemical References

• Albumins
• Blood Glucose
• Pyrroles
• Sodium-Glucose Transporter 2
• Sodium-Glucose Transporter 2 Inhibitors
• Sulfones
• Sodium
• Creatinine
• esaxerenone
• Potassium

Topics

• Albumins
• Albuminuria (complications, drug therapy)
• Blood Glucose
• Creatinine (urine)
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Diabetic Nephropathies (complications, drug therapy)
• Humans
• Potassium (therapeutic use)
• Pyrroles
• Sodium
• Sodium-Glucose Transporter 2
• Sodium-Glucose Transporter 2 Inhibitors (therapeutic use)
• Sulfones