Diuretic Effects of Sodium Glucose Cotransporter 2 Inhibitors and Their Influence on the Renin-Angiotensin System

Tuba M Ansary, Daisuke Nakano, Akira Nishiyama, Tuba M Ansary, Daisuke Nakano, Akira Nishiyama

Abstract

The renin-angiotensin system (RAS) plays an important role in regulating body fluids and blood pressure. However, inappropriate activation of the RAS contributes to the pathogenesis of cardiovascular and renal diseases. Recently, sodium glucose cotransporter 2 (SGLT2) inhibitors have been used as anti-diabetic agents. SGLT2 inhibitors induce glycosuria and improve hyperglycemia by inhibiting urinary reabsorption of glucose. However, in the early stages of treatment, these inhibitors frequently cause polyuria and natriuresis, which potentially activate the RAS. Nevertheless, the effects of SGLT2 inhibitors on RAS activity are not straightforward. Available data indicate that treatment with SGLT2 inhibitors transiently activates the systemic RAS in type 2 diabetic patients, but not the intrarenal RAS. In this review article, we summarize current evidence of the diuretic effects of SGLT2 inhibitors and their influence on RAS activity.

Keywords: diuretic effect; natriuresis; renin-angiotensin system (RAS); sodium glucose cotransporter 2 (SGLT2) inhibitor; type 2 diabetes.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Figures

Figure 1
Figure 1
Possible mechanisms by which SGLT2 inhibitors influence the systemic and intrarenal RAS. SGLT2 inhibitors transiently increase plasma renin activity acutely through osmotic diuresis. Meanwhile, SGLT2 inhibitors decrease renal AGT expression by reducing glucose levels in the kidney. However, SGLT2 inhibitors can increase the glucose load in distal proximal tubule and that might increase the AGT production. SGLT2, sodium-glucose cotransporter 2; RAS, renin-angiotensin system; AGT, angiotensinogen. ↑, increase; ↓, decrease; →, no change; +, in case of plasma volume compensation; −, in case of no plasma volume compensation.

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