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Updated: Jan 7, 2026

Multilevel Microdissection and Functional-Structural Profiling of Human Renal Arterial Branches
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Multilevel Microdissection and Functional-Structural Profiling of Human Renal Arterial Branches

Published on: September 5, 2025

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SGLT2 Inhibitors Confer Cardiovascular Protection via the Gut-Kidney-Heart Axis: Mechanisms and Translational

Yimei Tao1, Ning Zhang2, Zhaoxiang Wang2

  • 1Department of Endocrinology, Gusu School, Nanjing Medical University, The First People's Hospital of Kunshan, Kunshan 215300, China.

Journal of Cardiovascular Development and Disease
|December 24, 2025
PubMed

Insights

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefit heart and kidney health by improving the gut microbiome. These drugs modulate the gut-kidney-heart axis, reducing inflammation and metabolic stress for cardiorenal protection.

Area of Science:

  • Pharmacology
  • Microbiology
  • Cardiology
  • Nephrology

Background:

  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i) offer cardiovascular and renal benefits beyond glucose lowering.
  • The gut-kidney-heart axis, involving gut dysbiosis and inflammation, contributes to cardiorenal injury.
  • Integrated mechanisms of SGLT2i action on this axis are not fully understood.

Purpose of the Study:

  • To systematically review how SGLT2i modulate the gut-kidney-heart axis.
  • To integrate microecological, metabolic, and cross-organ protective effects of SGLT2i.
  • To propose a novel framework for understanding SGLT2i mechanisms.

Main Methods:

  • Systematic review of literature on SGLT2i and the gut-kidney-heart axis.
  • Analysis of SGLT2i effects on gut microbiota composition and function.
  • Evaluation of SGLT2i impact on metabolite profiles and intestinal barrier integrity.

Main Results:

  • SGLT2i reshape gut microbiota, promoting beneficial bacteria and suppressing harmful ones.
  • SGLT2i restore intestinal barrier integrity and regulate bile acid metabolism.
  • These effects reduce systemic inflammation, metabolic stress, and myocardial remodeling.

Conclusions:

  • SGLT2i exert cardiorenal protection by modulating the gut-kidney-heart axis through multi-level interventions.
  • A unified framework highlights "three-axis convergence to the heart" via microecological and metabolic regulation.
  • Future research should explore microbiota-targeted therapies and SGLT2i applications in non-diabetic populations.
Keywords:
SGLT2 inhibitorscardiovascular protectiongut microbiotagut-kidney-heart axismetabolic reprogramming

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