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Cardiovascular Protection by Sodium Glucose Cotransporter 2 Inhibitors: Potential Mechanisms

Bart Staels1

  • 1Université Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France.

The American Journal of Medicine
|May 21, 2017
PubMed

Insights

The exact mechanism empagliflozin uses to reduce cardiovascular events in type 2 diabetes patients is unknown. Hypotheses include hemodynamic, metabolic, and hormonal effects, rather than antiatherosclerotic actions.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial demonstrated reduced cardiovascular mortality in type 2 diabetes mellitus patients with high cardiovascular risk treated with empagliflozin versus placebo.
  • The precise mechanism underlying these cardioprotective effects remains to be elucidated.

Purpose of the Study:

  • To review and discuss the primary hypotheses proposed to explain the cardiovascular benefits of empagliflozin observed in the EMPA-REG OUTCOME trial.

Main Methods:

  • This review synthesizes current scientific literature and proposed mechanisms related to empagliflozin's action.
  • It evaluates the plausibility of various proposed mechanisms, including antiatherosclerotic, hemodynamic, metabolic, and hormonal effects.

Main Results:

  • An antiatherosclerotic effect is considered unlikely due to the rapid onset of cardiovascular mortality reduction.
  • Hemodynamic effects, such as decreased blood pressure and intravascular volume via osmotic diuresis, are considered more plausible.
  • Metabolic effects on cardiac fuel energetics and hormonal effects, like increased glucagon release, are also discussed as potential contributors.

Conclusions:

  • The cardioprotective mechanism of empagliflozin is multifactorial and not fully understood.
  • Hemodynamic and metabolic pathways are considered more likely contributors than direct antiatherosclerotic effects.
Keywords:
Cardiovascular outcomesEmpagliflozinMechanismsSodium glucose cotransporter 2 inhibitors

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