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Can sodium-glucose cotransporter 2 inhibitors 'spin the thread of life'?

Giuseppe Maltese1, Theocharis Koufakis2, Kalliopi Kotsa2

  • 1School of Cardiovascular Medicine and Sciences, King's College London, London, UK; Department of Diabetes and Endocrinology, Epsom and St Helier University Hospitals, Surrey, UK.

Trends in Endocrinology and Metabolism: TEM
|November 10, 2022
PubMed

Insights

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) offer cardiovascular and renal benefits beyond glucose control. These SGLT2 inhibitors may promote longevity through anti-aging pathways, potentially involving soluble Klotho.

Area of Science:

  • Cardiovascular Medicine
  • Nephrology
  • Endocrinology

Background:

  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i) initially developed for diabetes management.
  • Recent trials show SGLT2i reduce cardiovascular-renal events and mortality in diverse populations.
  • Observed benefits extend beyond glucose lowering, suggesting novel mechanisms.

Purpose of the Study:

  • To explore the anti-aging and pro-longevity effects of SGLT2 inhibitors.
  • To investigate the role of soluble Klotho in mediating SGLT2i's cardio-renal benefits.

Main Methods:

  • Review of randomized clinical trials and proposed mechanisms of action for SGLT2 inhibitors.
  • Analysis of signaling pathways, including Nrf2 activation and antioxidant enzyme induction.
  • Exploration of the association between SGLT2i and soluble Klotho levels.

Main Results:

  • SGLT2i demonstrate significant cardio-renal protective effects.
  • These benefits are independent of glycemic control.
  • Potential anti-aging effects mediated by pathways like Nrf2 and antioxidant enzymes.

Conclusions:

  • SGLT2 inhibitors possess pleiotropic effects contributing to cardiovascular and renal health.
  • Soluble Klotho may be a key mediator of SGLT2i's pro-longevity and cardio-renal protective actions.
  • SGLT2i represent a promising therapeutic target for age-related cardio-renal diseases.
Keywords:
KlothoSGLT2iageinglongevitytype 2 diabetes

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