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The pleiotropic effects of SGLT2 inhibitors and their mechanism

Czech version

Authors: Emil Martinka
Authors‘ workplace: Národný endokrinologický a diabetologický ústav, n.o., Ľubochňa
Published in: Forum Diab 2026; 15(1): 71-75
Category: Review Article

Overview

SGLT2 inhibitors represent an important class of therapeutic agents whose effects extend beyond glycemic control and include a broad spectrum of pleiotropic actions. The most robust clinical evidence supports their cardiorenal benefits, particularly the reduction in hospitalizations for heart failure and slowing of chronic kidney disease progression, even in non-diabetic populations. Additionally, favorable metabolic and hemodynamic effects have been observed, including modest reductions in body weight, blood pressure, and serum uric acid levels. Proposed mechanistic explanations include metabolic reprogramming, enhanced ketogenesis, reduction of oxidative stress, and modulation of inflammatory and immunometabolic pathways, including inhibition of the NLRP3 inflammasome. However, these mechanisms are largely supported by experimental and translational data, and their precise contribution to clinical outcomes remains uncertain. SGLT2 inhibitors likely target multiple interconnected pathogenic pathways characteristic of the cardio-renal-hepato-metabolic syndrome. Further research is required to clarify the dominant mediators of their clinical benefits.

Keywords:

pleiotropic effects – SGLT2 inhibitors – cardiorenal protection

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