- Medicines and Healthcare products Regulatory Agency
- 26 June 2015
- Therapeutic area:
- Endocrinology, diabetology and metabolism
Test for raised ketones in patients with acidosis symptoms, even if plasma glucose levels are near-normal.
For updated information on this topic, see Drug Safety Update article published in April 2016.
When treating patients who are taking an SGLT2 inhibitor (canagliflozin, dapagliflozin or empagliflozin):
- test for raised ketones in patients with symptoms of diabetic ketoacidosis (DKA); omitting this test could delay diagnosis of DKA
- if you suspect DKA, stop SGLT2 inhibitor treatment
- if DKA is confirmed, take appropriate measures to correct the DKA and to monitor glucose levels
- inform patients of the symptoms and signs of DKA (see below); advise them to get immediate medical help if these occur
- be aware that SGLT2 inhibitors are not approved for treatment of type 1 diabetes
- please continue to report suspected side effects to SGLT2 inhibitors or any other medicines on a Yellow Card
Reports of diabetic acidosis
Sodium glucose co-transporter 2 (SGLT2) inhibitors are licensed for use in adults with type 2 diabetes to improve glycaemic control. Serious and life-threatening cases of DKA have been reported in patients taking SGLT2 inhibitors (canagliflozin, dapagliflozin or empagliflozin).
In several cases, blood glucose levels were only moderately elevated (eg <14 mmol/L or 250 mg/dL), which is atypical for DKA. This atypical presentation could delay diagnosis and treatment. Therefore inform patients of the signs and symptoms of DKA (eg nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness) and test for raised ketones in patients with these signs and symptoms.
Half of the cases occurred during the first 2 months of treatment. Some cases occurred shortly after stopping the SGLT2 inhibitor.
One third of the cases involved off-label use in patients with type 1 diabetes. We remind you that this drug class is not licensed for the treatment of type 1 diabetes.
The underlying mechanism for SGLT2 inhibitor-associated DKA has not been established. We are investigating this concern along with other EU medicines regulators. We will communicate further advice as appropriate once the investigation is complete.
SGLT2 inhibitors – medicines in this class
The SGLT2 inhibitors marketed in the UK are listed below. Click on the brand name to see the summary of product characteristics (SPC).
|Brand name||Active substance(s)|
|Forxiga▼||Dapagliflozin tablets (5 mg and 10 mg)|
|Xigduo▼||Dapagliflozin/metformin tablets (5 mg/850 mg and 5 mg/1000 mg)|
|Invokana▼||Canagliflozin tablets (100 mg and 300 mg)|
|Vokanamet▼||Canagliflozin/metformin tablets (50 mg/850 mg, 50 mg/1000 mg, 150mg/850mg, 150mg/1000mg)|
|Jardiance▼||Empagliflozin tablets (10 mg and 25 mg)|
European Medicines Agency announcement June 2015
Post-publication addition: letter sent to health professionals in July 2015
Article citation: Drug Safety Update Volume 8 issue 11 June 2015 1.
Published: 26 June 2015
Therapeutic area: Endocrinology, diabetology and metabolism