We were interested in the recent article in Diabetes Care by Umapathysivam et al. (1), who reported two cases of euglycemic ketoacidosis after introduction of sodium–glucose cotransporter 2 inhibitor (SGLT2i) for heart failure with reduced ejection fraction in patients without diabetes. Reporting such adverse events is especially important, because SGLT2i may play a role in the recent rise of mortality from hyperglycemic crises in the U.S. (2).
Interestingly, both patients described by Umapathysivam et al. were treated by glucocorticoids soon before the ketoacidosis occurred, but this was not commented on by the authors. Glucocorticoids are widely known to reduce insulin sensitivity; however, they also quickly reduce insulin secretion (3), which can contribute to diabetic ketoacidosis in some cases. To our knowledge, glucocorticoids have not been identified as possible triggers for euglycemic ketoacidosis induced by SGLT2i, but this complication was identified in individuals with diabetes. The use of glucocorticoids is limited in individuals with diabetes because these drugs have a well-known hyperglycemic effect. The use of SGLT2i in heart failure without diabetes is expanding, whereas prescribed medications often include glucocorticoids in this population (25.8% according to a recent Australian report [4]). Due to frequent acute asthma or exacerbated chronic obstructive pulmonary disease, high doses of glucocorticoids were applied to 10% of 164,494 patients hospitalized for heart failure in the report from Dharmarajan et al. (5).
Future case reports and surveys will tell us whether euglycemic ketoacidosis induced by SGLT2i adds to the numerous undesirable effects of glucocorticoids, but we suggest that in the meantime, clinicians should pay special attention when they prescribe these medications in subjects treated with SGLT2i.
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Duality of Interest. No potential conflicts of interest relevant to this article were reported.
