Dapagliflozin (Forxiga): no longer authorised for treatment of type 1 diabetes mellitus
The authorisation holder for dapagliflozin has withdrawn the indication for type 1 diabetes mellitus. The removal of the type 1 diabetes indication is not due to any new safety concerns and the other indications of dapagliflozin are unchanged.
Advice for healthcare professionals:
- dapagliflozin 5 mg is no longer authorised for the treatment of patients with type 1 diabetes mellitus
- the removal of the type 1 diabetes indication is not due to any new safety concerns and the other indications of dapagliflozin are unchanged
- dapagliflozin should be reviewed and discontinued in patients with type 1 diabetes by or in consultation with a physician specialised in diabetes care as soon as clinically practical
- after stopping dapagliflozin treatment, frequent blood glucose monitoring is recommended
- an increased insulin dose may be needed, which should be undertaken carefully to minimise the risk of hypoglycaemia or hyperglycaemia
- diabetic ketoacidosis is a known risk with use of dapagliflozin in all patients with diabetes, but it occurs more frequently in patients with type 1 diabetes than those with type 2 diabetes
- additional risk minimisation materials to mitigate the risks in patients with type 1 diabetes are no longer available
- report suspected adverse drug reactions associated with use of dapagliflozin on a Yellow Card
Advice for healthcare professionals to give to patients and carers:
- always seek advice from your doctor or diabetes team before making changes to your diabetes medicines
- the manufacturer of dapagliflozin (Forxiga) has voluntarily withdrawn its use in type 1 diabetes
- this decision was not linked to a new safety issue and other patients using dapagliflozin for type 2 diabetes, heart failure, or chronic kidney disease can continue taking their medicine as recommended by a healthcare professional
- if you take dapagliflozin for your type 1 diabetes, your specialist will help you safely discontinue this treatment – you will need to monitor your blood glucose levels more closely to prevent hypoglycaemia or hyperglycaemia in the transition
Dapagliflozin indications
Sodium glucose co-transporter 2 (SGLT2) inhibitors act to improve glycaemic control by reducing glucose reabsorption and increasing urinary glucose excretion. The SGLT2 inhibitor dapagliflozin has been indicated for the treatment of type 2 diabetes since 2012 and is also indicated in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction and for the treatment of chronic kidney disease. For the full indications, see the Summary of Product Characteristics (SmPC).
Dapagliflozin (Forxiga) was authorised in 2019 as an adjunct to insulin in patients with type 1 diabetes with a body-mass index (BMI) of 27 kg per m2 or higher, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy.
Withdrawal of type 1 diabetes indication
On 25 October 2021, the marketing authorisation holder for dapagliflozin withdrew the indication for type 1 diabetes across Europe and in the UK. A letter was sent to UK healthcare professionals to inform them of the withdrawal. As such, patients with type 1 diabetes should discontinue dapagliflozin 5mg in consultation with their specialist diabetes physician as soon as clinically practical.
Dapagliflozin has a diuretic effect and has been associated with a decrease in blood pressure. It should therefore be noted that a small increase in blood pressure may be seen upon discontinuation of dapagliflozin.
Dapagliflozin was the only SGLT2 inhibitor that was available for treatment of type 1 diabetes.
The use of dapagliflozin 5mg for the treatment of type 1 diabetes required specific additional risk minimisation measures for the risk of diabetic ketoacidosis, including a patient alert card and a healthcare professional guide. This reflected the increased risk in type 1 compared with type 2 diabetes, with studies in type 1 diabetes reporting diabetic ketoacidosis with a common frequency (may affect up to 1 in 10 patients), and cases reported of euglycaemic diabetic ketoacidosis. As a result of the indication removal, the additional risk minimisation materials are no longer available.
The decision by the marketing authorisation holder to voluntarily withdraw the indication in type 1 diabetes followed commercial considerations due to a specific European-wide regulatory requirement for this authorisation. The decision was not driven by any new safety concerns, such as the already known increased risk of diabetic ketoacidosis in type 1 diabetes compared with type 2 diabetes.
Other indications for dapagliflozin 5mg and 10mg are not affected by this licensing change and both strengths will remain on the market. Dapagliflozin remains authorised in adults for the treatment of type 2 diabetes, for the treatment of symptomatic chronic heart failure with reduced ejection fraction, and for the treatment of chronic kidney disease.
Guidance should be consulted on prescribers’ responsibilities if using a medicine off-label or using an unlicensed medicine. For any use of SGLT2 inhibitors, follow advice on the risk of diabetic ketoacidosis in the product information, and consult past Drug Safety Update advice on minimising the risk of diabetic ketoacidosis with use of SGLT2 inhibitors in type 2 diabetes and monitoring ketones during treatment interruption due to surgery or acute illness.
Report suspected reactions on a Yellow Card
Suspected adverse drug reactions associated with dapagliflozin should be reported to the Yellow Card scheme. Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:
- the Yellow Card website
- the Yellow Card app; download from the Apple App Store or Google Play Store
- some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)
When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.
Report suspected side effects to medicines, vaccines, medical device and test kit incidents used in coronavirus (COVID-19) testing and treatment using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app. See the MHRA website for the latest information on medicines and vaccines for COVID-19.
Article citation: Drug Safety Update volume 15, issue 5: December 2021: 3.