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03-02-2025 | Ketoacidosis | Understanding the Disease

Understanding the disease: euglycemic ketoacidosis with SGLT2 inhibitors

Authors: Jolan Malherbe, Damien du Cheyron, Xavier Valette

Published in: Intensive Care Medicine

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Excerpt

Sodium–glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of drugs increasingly prescribed over the last decade. To date, four different molecules are available in the European countries: empagliflozin, dapagliflozin, canagliflozin and ertugliflozin. In clinical trials, gliflozins were proved to decrease cardiovascular mortality, heart failure or kidney disease progression [1]. Use of gliflozins is now a class Ia recommendation in type 2 diabetes [2], chronic kidney disease [3], and heart failure irrespective of the fraction of ejection [4, 5]. However, occurrence of diabetic ketoacidosis with use of gliflozins was reported early and European Medicines Agency warned as soon as 2016 about the risk of “atypical” diabetic ketoacidosis with use of SGLT2 inhibitors with normal of mildly elevated blood sugar levels, which may delay both diagnosis and treatment [6, 7]. Clinical benefits of gliflozins are well known in the intensive care community but the risk of euglycemic ketoacidosis remains under-reported as its true incidence may be higher than reported in clinical trials [810]. In cohort studies, SGLT2 inhibitors were associated with a twofold increased risk of diabetic ketoacidosis (DKA) as compared with glucagon-like peptide 1 receptor agonists, and a threefold increase as compared with dipeptidyl peptidase 4 inhibitors [11, 12]. Moreover, a recent network meta-analysis of 36 randomized controlled trials including 138,322 patients found an increased risk of DKA with SGLT2 inhibitors (odds ratio 2.07, high certainty of evidence)[13]. Considering the increasing amount of gliflozins prescriptions, and the specific features of this metabolic acidosis occurring despite normal or mildly elevated blood glucose levels, euglycemic ketoacidosis would probably represent a frequent but challenging diagnosis in a near future. Therefore, knowledge of this condition appears to be critical for ICU physicians. …
Literature
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go back to reference McDonagh TA, Metra M, Adamo M et al (2024) 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology (ESC) With the special contribution of the heart failure association (HFA) of the ESC. Eur Heart J 45:53–53. https://doi.org/10.1093/eurheartj/ehad613CrossRef McDonagh TA, Metra M, Adamo M et al (2024) 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology (ESC) With the special contribution of the heart failure association (HFA) of the ESC. Eur Heart J 45:53–53. https://​doi.​org/​10.​1093/​eurheartj/​ehad613CrossRef
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go back to reference European Medicines Agency (2016) EMA confirms recommendations to minimise ketoacidosis risk with SGLT2 inhibitors for diabetes European Medicines Agency (2016) EMA confirms recommendations to minimise ketoacidosis risk with SGLT2 inhibitors for diabetes
Metadata
Title
Understanding the disease: euglycemic ketoacidosis with SGLT2 inhibitors
Authors
Jolan Malherbe
Damien du Cheyron
Xavier Valette
Publication date
03-02-2025
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-025-07806-3