Sodium-glucose co-transporter-2 inhibitors: peculiar "hybrid" diuretics that protect from target organ damage and cardiovascular events

Nutr Metab Cardiovasc Dis. 2020 Sep 24;30(10):1622-1632. doi: 10.1016/j.numecd.2020.05.030. Epub 2020 Jun 8.

Abstract

Aims: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been proven to lead to relevant cardiovascular benefits, regardless of glycemic control function. SGLT2i have on the one hand led to reduction in cardiovascular events such as heart failure and on the other hand to renal protection. Blood pressure reduction and kidney function play a central role in these outcomes. This focused review describes the main mechanisms and clinical aspects of SGLT2i.

Data synthesis: These drugs act on the proximal renal tubule and behave as diuretics with a "hybrid" mechanism, as they can favour both natriuresis and enhanced diuresis due to an osmotic effect dependent on glycosuria, resulting in blood pressure decrease. The exclusive peculiarity of these "diuretics", which distinguishes them from loop and thiazide diuretics, lies also in the activation of the tubule-glomerular feedback.

Conclusions: This mechanism, resulting in modulation of arterioles' tone and renin secretion, contributes to the favorable outcomes, suggesting a wider use of SGLT2i in internal medicine, nephrology and cardiology.

Keywords: Cardiovascular disease; Diuretics; Heart failure; Natriuresis; Renal protection; Sodium-glucose co-transporter-2 inhibitors; Tubule-glomerular feedback.

Publication types

  • Review

MeSH terms

  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / mortality
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Diuretics / adverse effects
  • Diuretics / therapeutic use*
  • Humans
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / physiopathology
  • Protective Factors
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Biomarkers
  • Blood Glucose
  • Diuretics
  • Sodium-Glucose Transporter 2 Inhibitors