Ongoing monitoring by the US Food and Drug Administration (FDA) highlights the need to be alert for atypical presentations of diabetic ketoacidosis (DKA) in patients prescribed sodium-glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 inhibitors such as dapagliflozin and empagliflozin are contained in the following medicines with a number of new combination products expected to be available soon.

  • Dapagliflozin (Forxiga®)
  • Dapagliflozin + metformin (Xigduo® XR)
  • Empagliflozin (Jardiance®)
  • Empagliflozin + metformin (Jardiamet®)

As of October 2017, a total of 122 cases of DKA occurring in patients taking SGLT2 inhibitors have been reported to the Therapeutic Goods Administration (TGA) via the Database of Adverse Event Notifications. DKA is a potentially life-threatening complication of diabetes associated with low levels of insulin. The condition usually presents with significant hyperglycaemia. However, patients taking SGLT2 inhibitors may have only mild to moderate elevations in glucose levels which could delay diagnosis. There are a number of risk factors for DKA that should be considered before initiating and continuing treatment with an SGLT2 inhibitor, including:

  • Surgery;
  • Acute illness;
  • Food and fluid restrictions;
  • Severe dehydration;
  • A sudden reduction in insulin dose;
  • Alcohol abuse;
  • Very low carbohydrate diet; and
  • Low β-cell function reserve.

Strategies that may be considered to reduce the incidence and severity of DKA include:

  • Maintaining a high level of suspicion of DKA in patients taking SGLT2 inhibitors;
  • Monitoring for DKA during therapy;
  • Withholding SGLT2 inhibitors during clinical situations known to increase the risk of DKA (e.g. major surgery, serious illness);
  • Immediately discontinue SGLT2 inhibitors if DKA is suspected or confirmed;
  • Do not rely on blood glucose levels if DKA is suspected in a patient taking an SGLT2 inhibitor; and
  • Immediately refer serum ketone levels >1.5mmol/L (or >0.6mmol/L in the perioperative period) to the treating medical officer.

References:

  1. Burke KR, Schumacher CA, Harpe SE. SGLT2 Inhibitors: A systematic review of diabetic ketoacidosis and related risk factors in the primary literature. Pharmacotherapy 2017; 37(2): 187-94.
  2. Department of Health. Database of Adverse Event Notifications – Medicines. Woden: Therapeutic Goods Administration; 2018.

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