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Randomized Trial Comparing SGLT2 Inhibition and Hydrochlorothiazide on Sympathetic Traffic in Type 2 Diabetes

Karsten Heusser1, Jens Tank1, André Diedrich2,3

  • 1Institute of Aerospace Medicine, German Aerospace Center, Cologne Germany.

Kidney International Reports
|November 29, 2023
PubMed
Abstract

Insights

Sodium glucose cotransporter 2 (SGLT2) inhibition with empagliflozin did not significantly alter muscle sympathetic nerve activity (MSNA) in type 2 diabetes mellitus patients. However, empagliflozin shifted the relationship between body weight loss and MSNA, suggesting SGLT2-specific actions may attenuate sympathetic excitation.

Area of Science:

  • Cardiology
  • Endocrinology
  • Nephrology

Background:

  • Sodium glucose cotransporter 2 (SGLT2) inhibitors may improve cardiovascular outcomes, potentially via reductions in sympathetic nervous system activity.
  • Understanding the specific effects of SGLT2 inhibition on sympathetic activity is crucial for discerning its cardiovascular benefits.

Purpose of the Study:

  • To investigate whether SGLT2 inhibition with empagliflozin (Empa) reduces muscle sympathetic nerve activity (MSNA) in patients with type 2 diabetes mellitus (T2DM).
  • To compare the effects of empagliflozin with hydrochlorothiazide (HCT) on MSNA to differentiate SGLT2-specific actions from responses to natriuresis.

Main Methods:

  • A randomized, double-blind, parallel study involving 41 patients with T2DM on metformin monotherapy.
  • Participants received either empagliflozin (25 mg/d) or hydrochlorothiazide (25 mg/d) for 6 weeks.
  • Muscle sympathetic nerve activity (MSNA) was assessed using peroneal microneurography, alongside blood pressure and metabolic biomarkers.

Main Results:

  • Both empagliflozin and hydrochlorothiazide induced volume depletion and decreased systolic blood pressure.
  • Empagliflozin resulted in greater body weight loss and improved glycemic control compared to hydrochlorothiazide.
  • Neither drug significantly changed MSNA, but empagliflozin shifted the negative correlation between body weight loss and MSNA, indicating a potential attenuation of sympathetic activation.

Conclusions:

  • Increased sodium excretion and subsequent weight loss may normally promote sympathetic activation.
  • SGLT2 inhibition with empagliflozin may attenuate sympathetic excitation despite natriuresis and weight loss, suggesting SGLT2-specific mechanisms contribute to cardiovascular benefits.
Keywords:
HCTcardiovascular regulationempagliflozinhemodynamicsmicroneurographysympathetic activity

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