Possible risk factors for the development of sodium-glucose co-transporter 2 inhibitor- associated diabetic ketoacidosis in type 2 diabetes


  • Kate West Department of Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
  • Lucy-Anne Webb Department of Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
  • Matthew Fenech Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK
  • Ketan Dhatariya Department of Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK




SGLT-2 inhibitors, diabetic ketoacidosis


Background: In the summer of 2015 the Food and Drug Administration and European Medicines Agency reported that over 100 cases of diabetic ketoacidosis (DKA) had been identified and issued a warning of increasing concerns of a possible link between sodium-glucose co-transporter 2 (SGLT-2) inhibitor use and the development of DKA. Several mechanisms for this have been postulated, but precisely what factors predispose individuals to develop DKA remain unknown.

Methods: We conducted a literature search on Pubmed and Ovid databases and Google Scholar and report a further case of DKA occurring in a patient with a 16-year history of type 2 diabetes 10 months after starting dapagliflozin.

Results: Very few cases of DKA occurring in type 2 diabetes have been reported. Most cases of DKA have occurred in patients with type 1 diabetes taking part in clinical trials or given the drug ‘off licence’. Several potential mechanisms for developing DKA have been postulated. In addition to these, we suggest that a prolonged history of type 2 diabetes may lead to reduced beta cell reserve, increasing the probability of developing DKA.

Conclusion: Despite the insulin-independent mode of action, SGLT-2 inhibitors are currently only licensed for use in type 2 diabetes. If the duration of diabetes is long and/or if insulin doses are reduced on initiation, clinicians and patients should be wary of signs of DKA. Until further data are available, unlicensed use in type 1 diabetes should be avoided.


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