Published: 10 December 2015

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SGLT2 Inhibitors and Diabetic Ketoacidosis

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Prescriber Update 36(4): 57-58
December 2015

Key Messages

  • Sodium glucose co-transporter 2 (SGLT2) inhibitors (dapagliflozin, empagliflozin, canagliflozin) have been associated with cases of diabetic ketoacidosis (DKA).
  • SGLT2 inhibitor-associated DKA may occur within the first few months of treatment and have an atypical presentation.
  •  Patients should be informed of the signs and symptoms of DKA and advised to seek immediate medical attention should they experience these symptoms.


A number of serious cases of diabetic ketoacidosis (DKA) have been reported in patients taking sodium glucose co-transporter 2 (SGLT2) inhibitors (dapagliflozin, empagliflozin, canagliflozin) for type 2 diabetes1. Up to half the reported cases occurred during the first two months of treatment1.

DKA is usually associated with raised blood glucose levels. However, in a number of reported cases, patients presented atypically with only a slight increase in blood glucose levels.

Early signs and symptoms of ketoacidosis include difficulty breathing, nausea, vomiting, anorexia, excessive thirst, abdominal pain, confusion and unusual fatigue or sleepiness 1. More serious signs and symptoms include dehydration, deep gasping breathing, confusion and coma. Patients should be informed of these signs and symptoms and advised to seek immediate medical attention should they experience any of these symptoms.

To prevent delayed diagnosis, patients taking SGLT2 inhibitors with symptoms of acidosis should be tested for raised ketones, even if blood glucose levels are near normal. If ketoacidosis is suspected, treatment with SGLT2 inhibitors should be discontinued.

Internationally, DKA has also been associated with off-label use of SGLT2 inhibitors in patients with type 1 diabetes. Healthcare professionals are reminded that in New Zealand type 1 diabetes is not an approved indication for SGLT2 inhibitors.

Please continue to report any cases of diabetic ketoacidosis or other suspected adverse reactions associated with SGLT2 inhibitors to the Centre for Adverse Reactions Monitoring (CARM).

Further information can be found in the Dear Healthcare Professional letter distributed by AstraZeneca in July 2015 to inform prescribers of safety information regarding Forxiga (dapagliflozin)1.

References
  1. AstraZeneca Limited. 2015. Forxiga (Dapagliflozin) Dear Healthcare Professional Letter 9 July 2015. URL: www.medsafe.govt.nz/safety/DHCPLetters/Forxiga9July2014.pdf (accessed 17 November 2015).
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