Organ protection by SGLT2 inhibitors: role of metabolic energy and water conservation

Marton A, Kaneko T, Kovalik JP, Yasui A, Nishiyama A, Kitada K, Titze J (2020)

Publication Type: Journal article, Review article

Publication year: 2020

Journal

Nature Reviews Nephrology Nature Research

DOI: 10.1038/s41581-020-00350-x

Abstract

Therapeutic inhibition of the sodium–glucose co-transporter 2 (SGLT2) leads to substantial loss of energy (in the form of glucose) and additional solutes (in the form of Na+ and its accompanying anions) in urine. However, despite the continuously elevated solute excretion, long-term osmotic diuresis does not occur in humans with SGLT2 inhibition. Rather, patients on SGLT2 inhibitor therapy adjust to the reduction in energy availability and conserve water. The metabolic adaptations that are induced by SGLT2 inhibition are similar to those observed in aestivation — an evolutionarily conserved survival strategy that enables physiological adaptation to energy and water shortage. Aestivators exploit amino acids from muscle to produce glucose and fatty acid fuels. This endogenous energy supply chain is coupled with nitrogen transfer for organic osmolyte production, which allows parallel water conservation. Moreover, this process is often accompanied by a reduction in metabolic rate. By comparing aestivation metabolism with the fuel switches that occur during therapeutic SGLT2 inhibition, we suggest that SGLT2 inhibitors induce aestivation-like metabolic patterns, which may contribute to the improvements in cardiac and renal function observed with this class of therapeutics.

Authors with CRIS profile

Jens Titze Professur für Elektrolyt- und Kreislaufforschung

Involved external institutions

Duke-NUS Medical School / 杜克—国大医学研究生院 SG Singapore (SG) Nippon Boehringer Ingelheim Co Ltd. JP Japan (JP) Kagawa University JP Japan (JP)

How to cite

APA:

Marton, A., Kaneko, T., Kovalik, J.P., Yasui, A., Nishiyama, A., Kitada, K., & Titze, J. (2020). Organ protection by SGLT2 inhibitors: role of metabolic energy and water conservation. Nature Reviews Nephrology. https://dx.doi.org/10.1038/s41581-020-00350-x

MLA:

Marton, Adriana, et al. "Organ protection by SGLT2 inhibitors: role of metabolic energy and water conservation." Nature Reviews Nephrology (2020).

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