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Updated: Oct 8, 2025

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
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Sodium glucose cotransporter 1 (SGLT1) inhibitors in cardiovascular protection: Mechanism progresses and challenges

Yebei Li1, Gaosi Xu1

  • 1Department of Nephrology, the Second Affiliated Hospital of Nanchang University, China.

Pharmacological Research
|December 31, 2021
PubMed

Insights

Sodium glucose cotransporter 1 (SGLT1) inhibitors show cardiovascular benefits, reducing deaths and heart failure hospitalizations. This review explores proposed mechanisms behind these protective effects for better clinical event reduction.

Area of Science:

  • Cardiology
  • Pharmacology
  • Biochemistry

Background:

  • Sodium glucose cotransporter 1 (SGLT1) inhibitors have demonstrated significant cardiovascular benefits in recent clinical trials.
  • These benefits include reduced cardiovascular mortality and heart failure hospitalizations across diverse patient populations, including those with and without diabetes or heart failure.

Purpose of the Study:

  • To review and synthesize proposed mechanisms underlying the cardiovascular protective effects of SGLT1 inhibitors.
  • To evaluate the advantages and disadvantages of these proposed mechanisms.
  • To prioritize mechanisms most relevant to the observed reduction in clinical cardiovascular events.

Main Methods:

  • Literature review of clinical trials and proposed mechanistic studies on SGLT1 inhibitors.
  • Analysis and comparison of proposed cardiovascular protective mechanisms.
  • Synthesis and prioritization of mechanisms based on their potential contribution to clinical outcomes.

Main Results:

  • Multiple potential mechanisms contribute to SGLT1 inhibitor cardiovascular benefits.
  • Proposed mechanisms include reduced oxidative stress, improved cardiac glucose uptake, protection against ischemia/reperfusion injury, and modulation of cardiac cell functions (fibroblast activation, apoptosis, pyroptosis, hypertrophy).
  • Mechanisms also encompass improved ventricular function and reduced arrhythmia susceptibility.

Conclusions:

  • The precise mechanisms of SGLT1 inhibitor cardiovascular protection require further elucidation.
  • Synthesizing proposed mechanisms suggests a multi-faceted approach to cardiovascular benefit.
  • Prioritizing mechanisms linked to clinical event reduction is crucial for future research and therapeutic development.
Keywords:
Diabetic cardiomyopathyHeart failureIschemia/reperfusion injuryReactive oxygen speciesSGLT1 inhibitorSodium glucose cotransporter 1

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