The DKA that wasn't: a case of euglycemic diabetic ketoacidosis due to empagliflozin

Abstract

Sodium glucose co-transporter (SGLT-2) inhibitor is a relatively new medication used to treat diabetes. At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class. Risk factors for the development of ketoacidosis among patients who take SGLT-2 inhibitors include decrease carbohydrate intake/starvation, acute illness and decrease in insulin dose. When identified, immediate cessation of the medication and administration of glucose must be done, and in some instances, starting an insulin drip might be necessary. We present a case of a patient with diabetes mellitus being on empagliflozin (SGLT-2 antagonist) who was admitted for acute cholecystitis. The hospital course was complicated by euglycemic diabetic ketoacidosis after being kept nothing per orem before a contemplated cholecystectomy.

Dapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials

“…Post‐marketing reports of SGLT2 inhibitor‐associated ketoacidosis resulted in the FDA issuing a safety communication concerning euglycaemic ketoacidosis in patients receiving SGLT2 inhibitors. The American Association of Clinical Endocrinologists and American College of Endocrinology subsequently released a position statement that highlighted the need to fully understand the mechanisms of the metabolic effect of SGLT2 inhibitors, with a focus on analysing the potential problem of DKA with lower‐than‐anticipated glucose levels.…”

Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature

“…We retrieved a total of 105 episodes of DKA in patients receiving SGLT2i from May 2014 to April 2017 . Demographic characteristics, type of diabetes and type of SGLT2i are reported in Table .…”

A Case of Euglycemic Diabetic Ketoacidosis due to Canagliflozin Complicated by Takotsubo Cardiomyopathy

“…Canagliflozin, dapagliflozin and empaglifilozin are the SGLT-2 inhibitors currently approved by the FDA [2]. Canagliflozin decreases the renal threshold for glucose excretion by reversibly blocking SGLT 2 located in the proximal convoluted tubule of the kidney and thus increases loss of glucose in the urine thereby decreasing serum glucose concentration [3].…”

“…The fall in the blood glucose level as glucose is lost in the urine decreases the insulin level in the body and increases glucagon level thus favoring gluconeogenesis and ketogenesis [10]. Decrease in the Insulin or secretagouge dose, starvation and acute illness have been identified as risk factors for euglycemic DKA as these conditions increase the counter regulatory hormones including cortisol, glucagon and epinephrine which promotes ketogenesis [2,11]. Given reduced oral intake and concurrent HCAP, acute illness and starvation might have played a role in activating the ketosis pathway in our patient.…”

“…Major adverse effect of SGLT-2 inhibitors is to increase the propensity towards ketoacidosis with lower than anticipated blood glucose level although the incidence of DKA has not found to be greater than the general diabetes population [6]. It has been proposed that acute illness, starvation, deficiency of insulin or oral secretagouges increases the release of counter regulatory hormones that promotes gluconeogenesis and ketogenesis [2,11]. SGLT-2 inhibition is reversed quickly after cessation of SGLT-2 inhibitors.…”