Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition

By A. Peters, Elizabeth O. Buschur, John B. Buse, P. Cohan, J. Diner, I. Hirsch. Diabetes Care, 2015

760 citations recorded by the source corpus.

OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS Cases identified incidentally are described. RESULTS We identified 13 episodes of SGLT-2 inhibitor–associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers. CONCLUSIONS SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes.

Subfields: Endocrinology, Diabetes and Metabolism, Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/67f8f6f9431115921016303edaf0e1a66df11ec9

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Citations in the corpus

Shift to Fatty Substrate Utilization in Response to Sodium–Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes (2016, neutral): “RaOAUC (g $ h) 61 (14) 62 (15) 63 (12) 58 (15) 57 (11) 59 (19)”
CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY. (2016, background): “Investigations into postmarketing reports of SGLT-2 inhibitor–associated diabetic ketoacidosis (DKA), which has been reported to occur in type 1 diabetes and T2D patients with less than expected hyperglycemia (euglycemic DKA) (98), are ongoing.”
Empagliflozin for Type 2 Diabetes Mellitus: An Overview of Phase 3 Clinical Trials (2017, background): “, euglycemic ketoacidosis), which is not typical in DKA [64].”
Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors (2015, background): “(4) exemplify some of the factors that triggered DKA: most commonly they were”