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SGLT2 Inhibitors and Diabetic Kidney Disease: Targeting Multiple and Interrelated Signaling Pathways for Renal

Georgios Papaetis1,2

  • 1K.M.P THERAPIS Paphos Medical Center, Internal Medicine and Diabetes Clinic, 14 Vasileos Georgiou B Street, Office 201, 8010, Paphos, Cyprus.

Current Molecular Pharmacology
|October 31, 2023
PubMed

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors offer significant benefits for diabetic kidney disease patients. These drugs improve kidney health through multiple pathways beyond blood sugar control, reducing mortality risks.

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Diabetic kidney disease affects 20-40% of diabetes patients, increasing mortality.
  • Multiple pathophysiological mechanisms drive diabetic kidney disease progression.
  • There is a critical need for multitarget therapies.

Purpose of the Study:

  • To investigate the mechanisms underlying the renal benefits of SGLT2 inhibitors in diabetic patients.
  • To explore the role of SGLT2 inhibitors in managing chronic kidney disease progression.
  • To highlight the multitarget therapeutic potential of SGLT2 inhibitors.

Main Methods:

  • Review of in vitro studies, exploratory research, and randomized controlled trial sub-analyses.
  • Analysis of biomarker investigations.
  • Focus on cellular and molecular pathways affected by SGLT2 inhibitors.

Main Results:

  • SGLT2 inhibitors demonstrate beneficial renal activities independent of antihyperglycemic effects.
  • Key mechanisms include reduced intraglomerular pressure, TGF restoration, and RAAS modulation.
  • Improvements observed in renal hypoxia, metabolism, mitochondrial function, inflammation, oxidative stress, and fibrosis.

Conclusions:

  • SGLT2 inhibitors represent a practice-changing therapy for type 2 diabetes and diabetic kidney disease.
  • Their multitarget actions offer a promising strategy for ameliorating chronic kidney disease evolution.
  • Understanding these mechanisms is crucial for optimizing SGLT2 inhibitor use in diabetes management.
Keywords:
AlbuminuriaChronic kidney diseaseGlucosuriaSGLT2 inhibitorsTGFTGFType 2 diabetesType 2 diabetes

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