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5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
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SGLT2 Inhibition for Cardiovascular Diseases, Chronic Kidney Disease, and NAFLD

Moein Ala1

  • 1School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

Endocrinology
|August 3, 2021
PubMed

Insights

Sodium glucose cotransporter 2 (SGLT-2) inhibitors offer significant benefits beyond diabetes management. These drugs improve cardiovascular and renal health by reducing inflammation and fibrogenesis.

Area of Science:

  • Pharmacology
  • Cardiovascular Medicine
  • Nephrology
  • Hepatology

Background:

  • Sodium glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic drugs.
  • SGLT-2 plays a role in inflammation, fibrogenesis, and cellular signaling.
  • Existing research indicates SGLT-2 inhibitors have organ-protective effects.

Purpose of the Study:

  • To review the beneficial effects of SGLT-2 inhibitors on nonalcoholic fatty liver disease (NAFLD), cardiovascular diseases, and renal diseases.
  • To elucidate the molecular mechanisms underlying these beneficial effects.

Main Methods:

  • This is a narrative review.
  • The review synthesizes findings from animal studies, observational studies, clinical trials, and meta-analyses.
  • Molecular mechanisms are dissected in detail.

Main Results:

  • SGLT-2 inhibitors attenuate inflammation and fibrogenesis, improving organ function.
  • They reduce blood pressure, improve lipid profiles, and aid in weight management.
  • Benefits extend to heart failure, arrhythmias, ischemic heart disease, NAFLD, chronic kidney disease, and acute kidney injury.
  • Improved cardiovascular and all-cause mortality are associated with SGLT-2 inhibitors.
  • They improve micro- and macroalbuminuria.
  • SGLT-2 inhibitors modulate signaling pathways, enhancing lipolysis, ketogenesis, mitochondrial biogenesis, and autophagy.
  • They attenuate the renin-angiotensin-aldosterone system, lipogenesis, endoplasmic reticulum stress, oxidative stress, apoptosis, and fibrogenesis.

Conclusions:

  • SGLT-2 inhibitors demonstrate broad therapeutic benefits for metabolic and organ-specific diseases.
  • Their mechanisms involve reprogramming key cellular signaling pathways.
  • Further research into these mechanisms can optimize treatment strategies for NAFLD, cardiovascular, and renal diseases.
Keywords:
SGLT-2 inhibitorsautophagyfibrosisinflammationketogenesismolecular mechanism

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