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The Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering

Pasquale Pignatelli1,2, Francesco Baratta1, Raffaella Buzzetti3

  • 1Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy.

Antioxidants (Basel, Switzerland)
|October 27, 2022
PubMed

Insights

Sodium-glucose co-transporter-2 inhibitors (gliflozins) reduce oxidative stress and platelet activation in type 2 diabetes patients. These findings suggest gliflozins offer cardiovascular protection by inhibiting thrombus formation.

Area of Science:

  • Cardiovascular Medicine
  • Endocrinology
  • Pharmacology

Background:

  • Sodium-glucose co-transporter-2 inhibitors (gliflozins) are a novel anti-hyperglycemic class with established cardioprotective effects in type 2 diabetes (T2D).
  • Platelet activation and oxidative stress are critical contributors to atherothrombotic complications.

Purpose of the Study:

  • To investigate the effects of gliflozins on oxidative stress, platelet activation, and thrombus formation in patients with T2D.
  • To explore potential mechanisms underlying the cardiovascular benefits of gliflozins.

Main Methods:

  • An interventional, open-label, single-arm before-after study involving 32 T2D patients on metformin therapy.
  • Assessment of oxidative stress markers (sNOX2-dp, H2O2), platelet activation markers (TxB2, sP-selectin, sCD40L), and thrombus formation before and after 15 days of gliflozin treatment.
  • An in vitro study using stimulated platelets treated with gliflozins.

Main Results:

  • Gliflozin treatment significantly reduced oxidative stress markers (sNOX2-dp, H2O2) and platelet activation markers (TxB2, sP-selectin, sCD40L) compared to baseline.
  • A significant reduction in thrombus formation and potentiation of anti-oxidant power (HBA) were observed with gliflozin treatment.
  • In vitro studies confirmed that gliflozins decrease oxidative stress, platelet activation, and thrombus growth.

Conclusions:

  • Gliflozins possess significant antiplatelet and antithrombic activity in T2D patients.
  • These effects are associated with down-regulation of NOX2, suggesting a novel mechanism for gliflozin-mediated cardiovascular protection.
Keywords:
gliflozinsoxidative stressplatelet activationthrombosistype 2 diabetes

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