Ketones: the double-edged sword of SGLT2 inhibitors? – published online 16/10/2022

Beatrice C. Lupsa, Richard G. Kibbey, Silvio E. Inzucchi

Sodium−glucose cotransporter 2 (SGLT2) inhibitors are a relatively recent class of glucose-lowering medication, originally approved for treating individuals with type 2 diabetes, that have been found to have cardiovascular and renal benefits, independent of their glucose-lowering effect. The mechanisms underlying these salutary effects remain unclear. In this issue, Lupsa et al (https://doi.org/10.1007/s00125-022-05815-1) provide a comprehensive review of the advantages of SGLT2 inhibitors on cardiac and kidney outcomes and the potential role of elevated plasma ketone levels in mediating these benefits. The impact of SGLT2 inhibitors on ketone physiology is reviewed and the risk of ‘euglycaemic’ diabetic ketoacidosis is additionally explored. The topic of ketogenesis and SGLT2 inhibitors is of both scientific and clinical significance.

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