SGLT2 inhibitors: New warnings!

By: Ph. Mohammad Al- Roomi      


Information on potential risk of toe amputation to be included in prescribing information


The European Medicines Agency (EMA) panel has determined that a warning stating that the sodium glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes may increase the risk for lower-limb amputation should be included in the prescribing information for all drugs in this class. Two clinical trials, CANVAS and CNAVAS-R, have been conducted and found this risk.


Information for healthcare professionals:

  • An increase in lower limb amputation (mostly affecting the toes) has been observed in two long-term clinical trials, CANVAS and CANVAS-R, in patients taking canagliflozin (Invokana,Vokanamet, Janssen)compared with those taking placebo. The studies, which are still ongoing, involved patients at high cardiovascular risk.
  • Although an increase in amputations has not been seen in studies with other SGLT2 inhibitors, dapagliflozin (Farxiga, XigduoXR, Ebymect, Edistride, Qtern, AstraZeneca) and empagliflozin (Jardiance, Glyxambi, Synjardy, BoehringerIngelheim), data available to date are limited and the risk may also apply to these other medicines.
  • The underlying mechanism by which canagliflozin may increase the risk of amputation has not been established and no risk factors apart from general risk factors for amputation have been identified.
  • As a precaution, patients taking an SGLT2-inhibitor should be counselled about the importance of routine preventative foot care.
  • For canagliflozin, consideration should also be given to carefully monitoring patients at higher risk of amputation and counselling them about the importance of maintaining adequate hydration.
  • Consideration may be given to stopping treatment with canagliflozin in patients who develop events preceding amputation such as lower-extremity skin ulcer, infection, osteomyelitis or gangrene.


Information for patients:

  • All patients with diabetes are at increased risk of infection and sores which can lead to amputations.
  • If you are taking medicines containing canagliflozin, dapagliflozin and empagliflozin to treat your type 2 diabetes, it is particularly important that you check your feet regularly and follow your doctor’s advice on routine preventative foot care and adequate hydration.
  • Tell your doctor about any wounds or discoloration, or if your feet are tender or painful.
  • If you have any questions or concerns about your treatment, speak to your doctor, pharmacist or nurse.