The Food and Drug Administration has approved the use of sodium-glucose co-transporter 2 (SGLT-2) inhibitors for use in Type II diabetics. These are a relatively new addition to the armamentaria of diabetes management. Postmarketing surveillance is a witness to several side effects, a morbid one being ketoacidosis. Herein is discussed a scenario of a Type II diabetic who presented with substantial ketoacidosis without significant hyperglycemia. The absence of the customary precipitating factors and the presence of a recent introduction of canagliflozin, a SGLT-2 inhibitor to the diabetes prescription, hinted at the causal relationship. Of note, she had never experienced diabetic ketoacidosis in the past prior to commencement of SGLT-2 inhibitor therapy. As clinicians, we need to be aware of the treatment-emergent adverse effect of this relatively new class of diabetic treatment.
Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol 2013;1:140-51.
Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 2014;124:499-508.
Keller U, Schnell H, Sonnenberg GE, Gerber PP, Stauffacher W. Role of glucagon in enhancing ketone body production in ketotic diabetic man. Diabetes 1983;32:387-91.
Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: Possible mechanism and contributing factors. J Diabetes Investig 2016;7:135-8.
Taylor SI, Blau JE, Rother KI. SGLT2 inhibitors may predispose to ketoacidosis. J Clin Endocrinol Metab 2015;100:2849-52.
Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: A predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care 2015;38:1638-42.
Chao EC. SGLT-2 inhibitors: A new mechanism for Glycemic control. Clin Diabetes 2014;32:4-11.
Handelsman Y, Henry RR, Bloomgarden ZT, Dagogo-Jack S, DeFronzo RA, Einhorn D, et al. American association of clinical endocrinologists and American college of endocrinology position statement on the association of sglt-2 inhibitors and diabetic ketoacidosis. Endocr Pract 2016;22:753-62.
US Food and Drug Administration. FDA Drug Safety Communication: FDA Warns that SGLT2 Inhibitors for Diabetes May Result in a Serious Condition of too Much Acid in the Blood. Available from: http://www.fda.gov/drugs/drugsafety/ucm446845.htm. [Last accessed on 2015 May 15].
Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB, et al. Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care 2015;38:1687-93.