MHRA published a Drug Safety Update in March 2017 detailing the increased risk of lower limb amputation, mostly affecting the toes, with the sodium-glucose co-transporter 2 (SGLT2) inhibitors.
SGLT2 inhibitors are licensed for the treatment of adults with type 2 diabetes, either as monotherapy or in combination with other glucose lowering drugs, where diet and exercise alone have not provided adequate glycaemic control.
The following SGLT2 inhibitors are currently available within the UK:
- Canagliflozin (Invokana)
- Dapagliflozin (Forxiga)
- Empagliflozin (Jardiance)
In June 2016 a Drug Safety Update was published to highlight the increased risks of lower limb amputations with canagliflozin when compared to placebo.
A subsequent review of the risks of amputation in patients taking SGLT2 inhibitors by the EMA noted that diabetic patients, especially those with poor glycaemic control or pre-existing cardiovascular conditions are at an increased risk of infection and ulcers that predispose the patient to amputation.
The precise mechanism by which canagliflozin increases the risk of amputation is unclear, and whilst the increased risk has not yet been seen in studies of dapagliflozin or empagliflozin the risk could also apply to these drugs.
Healthcare professionals have been advised to:
- Carefully monitor patients prescribed canagliflozin who have risk factors for amputation e.g. poor glycaemic control or existing cardiovascular disease.
- Consider stopping canagliflozin in patients who develop foot complications such as infection, skin ulcers, osteomyelitis or gangrene.
- Patients prescribed SGLT2 inhibitors should be counselled about the importance of adequate foot care and hydration.
- Standard treatment guidelines should be followed for the routine foot care of patients with diabetes.
- Suspected side effects with SGLT2 inhibitors should be reported on a yellow card.
Pharmacists should also be prepared to respond to patient queries following revisions to the Patient Information Leaflets of these products to include a warning on the potential increased risk of lower limb amputations.