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 [
8‐
10]. 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. …