The European Medicines Agency (EMA) is informing about a potential increased risk of lower limb amputation in patients taking the SGLT2 inhibitors canagliflozin, dapagliflozin and empagliflozin used for type 2 diabetes.
Patients taking these medicines are reminded to check their feet regularly and follow their doctor’s advice on routine precautionary foot care. They should also tell their doctor if they notice any wounds or discoloration, or if their feet are tender or painful.
The review of SGLT2 inhibitors was impelled by an increase in lower limb amputations (mostly affecting the toes) in patients taking canagliflozin in two clinical trials, CANVAS and CANVAS-R. The studies, which are still ongoing, involved patients at high risk of heart problems and matched canagliflozin with placebo (a dummy treatment).
All patients with diabetes (especially those with poorly controlled diabetes and problems with the heart and blood vessels) are at higher risk of infection and ulcers (sores) which can lead to amputations. The mechanism by which canagliflozin may increase the risk of amputation is still unclear.
A rise in lower limb amputations has not been seen in studies with other medicines in the same class, dapagliflozin and empagliflozin. However, data available to date are limited and the risk may also apply to these other medicines.
Further data are anticipated from ongoing studies with canagliflozin, dapagliflozin and empagliflozin.
A warning of the potential increased risk of toe amputation will be included in the recommending information for these medicines. For canagliflozin, the commending information will also list lower limb amputation as an uncommon side effect (occurring in between 1 and 10 patients in 1,000). Doctors may consider stopping treatment with canagliflozin if patients develop significant foot complications such as infection or skin ulcers.
The review of SGLT2 inhibitors was approved out by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC approvals have now been certified by the Committee for Medicinal Products for Human Use (CHMP), and will be sent to the European Commission for a final legally-binding decision valid throughout the EU.
Dated: 24 Feb 2017