SGLT2 inhibitors approved for T2DM only
Sodium glucose co-transporter 2 inhibitor products are approved for use in the management of type 2 diabetes mellitus - they are not approved for use in type 1 diabetes. Prescribers are reminded of the risk of diabetic ketoacidosis with the off-label use of these medicines.
Sodium glucose co-transporter 2 (SGLT2) inhibitors improve glycaemic control in patients with type 2 diabetes mellitus (T2DM) by reducing renal glucose reabsorption. Through inhibition of SGLT2 in these patients, excess glucose is excreted in the urine.
Due to continued local and international post-marketing reports of off-label use of SGLT2 inhibitors, the Therapeutic Goods Administration (TGA) is reminding health professionals that these products are approved for use in the management of T2DM only. They are not approved for use in patients with type 1 diabetes mellitus (T1DM).
This applies to the SGLT2 inhibitors empagliflozin, dapagliflozin, ertugliflozin and canagliflozin, marketed in Australia as Jardiance, Forxiga, Steglatro and Invokana, respectively.
The current Product Information (PI) for these medicines has not changed, and still includes lengthy warnings regarding the increased risk of diabetic ketoacidosis (DKA) with SGLT2 inhibitor use in T1DM.
Based on data with sotagliflozin in T1DM, the United States Food and Drug Administration (FDA) estimated an 8-fold increase in the risk of ketoacidosis with an additional case of ketoacidosis being observed for every 26 patient-years of adjunctive therapy.
Adverse events reported to the TGA
In 2021, the TGA received 6 reports of off-label use with SGLT2 inhibitors in T1DM patients. Of these, 3 were associated with DKA, indicating that off-label prescribing of SGLT2 inhibitors in T1DM continues. The TGA considers that the seriousness of the risk of DKA requires an updated reminder for prescribers about the risks of off-label use of SGLT2 inhibitors in T1DM patients.
Information for health professionals
The TGA previously published the following safety updates about SGTL2 inhibitors and the risk of DKA:
- August 2015 - TGA Safety Advisory - risk of diabetic ketoacidosis
- October 2015 - TGA MSU - SGLT2 inhibitors and diabetic ketoacidosis
- July 2018 - TGA Safety advisory - diabetic ketoacidosis and surgical procedures
In each of these safety updates, the TGA informed or reminded health professionals about the increased risk of DKA with T1DM. They also reiterated that SGTL2 inhibitors are not recommended for the treatment of T1DM.
Prescribers are again reminded that SGLT2 inhibitors should be used according to the PI, and T1DM is not an approved indication for these medicines.
What to report? You don't need to be certain, just suspicious!
The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.
We particularly request reports of:
- all suspected reactions to new medicines (look for the Black Triangle in PI and CMI documents - this symbol identifies medicines that are new or being used differently)
- all suspected medicines interactions
- suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.
Reports may be submitted:
Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, taking into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.
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For correspondence or further information about Medicines Safety Update, contact the TGA's Pharmacovigilance and Special Access Branch at ADR.Reports@tga.gov.au.
Medicines Safety Update is written by staff from the Pharmacovigilance Branch.
Editor: Dr Catherine Brogan
Deputy Editor: Mr Michael Pittman
Contributors: Dr Angela Gowland, Dr Rebecca Matthews