SGLT2 inhibitors
- Procedure started
- Under evaluation
- PRAC recommendation
- CHMP opinion
- European Commission final decision
Table of contents
Overview
EMA confirms recommendations to minimise ketoacidosis risk with SGLT2 inhibitors for diabetes
Healthcare professionals should be aware of possible atypical cases
On 25 February 2016, the European Medicines Agency (EMA) confirmed recommendations1 to minimise the risk of diabetic ketoacidosis in patients taking SGLT2 inhibitors (a class of type 2 diabetes medicines).
Diabetic ketoacidosis is a serious complication of diabetes caused by low insulin levels. Rare cases of this condition, including life-threatening ones, have occurred in patients taking SGLT2 inhibitors for type 2 diabetes and a number of these cases have been atypical, with patients not having blood sugar levels as high as expected.
An atypical presentation of diabetic ketoacidosis can delay diagnosis and treatment. Healthcare professionals should therefore consider the possibility of ketoacidosis in patients taking SGLT2 inhibitors who have symptoms consistent with the condition even if blood sugar levels are not high.
Following a review of the cases, EMA recommended updating the product information of SGLT2 inhibitors to list diabetic ketoacidosis as a rare adverse reaction (affecting up to 1 in 1,000 patients).
Patients taking these medicines should be aware of the symptoms of diabetic ketoacidosis, including rapid weight loss, nausea or vomiting, stomach pain, excessive thirst, fast and deep breathing, confusion, unusual sleepiness or tiredness, a sweet smell to the breath, a sweet or metallic taste in the mouth, or a different odour to urine or sweat. Patients should contact a doctor or the nearest hospital straightaway if they have any of these symptoms.
If diabetic ketoacidosis is suspected or confirmed, treatment with SGLT2 inhibitors should be stopped immediately and should not be re-started unless another cause for the ketoacidosis is identified and resolved.
Healthcare professionals should exercise caution with SGLT2 inhibitors in patients with risk factors for ketoacidosis and inform patients of these factors. These include low insulin-producing capacity in the pancreas, a sudden drop in a patient's insulin dose, increased insulin requirement (due to illness, surgery or alcohol abuse) or conditions that can restrict food intake or lead to severe dehydration.
In addition, EMA recommended temporarily stopping SGLT2 inhibitors in patients who are undergoing major surgery or are in hospital due to serious illness.
Finally, EMA reminded healthcare professionals that SGLT2 inhibitors are not authorised for type 1 diabetes, noting that cases of ketoacidosis have also occurred during off-label use and clinical trials in type 1 diabetes.
The benefits of these medicines continue to outweigh the risks in the treatment of type 2 diabetes.
EMA's recommendations are based on an initial review by its Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC recommendations were sent to the Committee for Medicinal Products for Human Use (CHMP), which confirmed them and adopted the Agency's final opinion.
The CHMP opinion was then sent to the European Commission, which issued a legally-binding decision valid throughout the EU.
1 PRAC recommendations issued on 11 February 2016
Key facts
About this medicine
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Approved name |
SGLT2 inhibitors
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International non-proprietary name (INN) or common name |
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Associated names |
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About this procedure
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Current status |
European Commission final decision
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Reference number |
EMEA/H/A-20/1419
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Type |
Article 20 procedures
This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of quality, safety or efficacy issues. |
Authorisation model |
Centrally authorised product(s)
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Decision making model |
PRAC-CHMP-EC
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Key dates and outcomes
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Procedure start date |
11/06/2015
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PRAC recommendation date |
11/02/2016
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CHMP opinion/CMDh position date |
25/02/2016
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EC decision date |
28/04/2016
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Outcome |
Risk minimisation measures
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All documents
Procedure started
SGLT2 inhibitors Article-20 procedure - Review started (PDF/77.83 KB)
First published: 12/06/2015
Last updated: 12/06/2015
EMA/390062/2015
SGLT2 inhibitors Article-20 procedure - Notification (PDF/39.03 KB)
First published: 12/06/2015
Last updated: 12/06/2015
EMEA/H/A-20/1419
SGLT2 inhibitors Article-20 procedure - Timetable for the procedure (PDF/69.32 KB)
First published: 12/06/2015
Last updated: 09/10/2015
EMA/PRAC/391289/2015
SGLT2 inhibitors Article-20 procedure - PRAC list of questions (PDF/94.32 KB)
First published: 12/06/2015
Last updated: 12/06/2015
EMA/PRAC/390892/2015
Recommendation provided by Pharmacovigilance Risk Assessment Committee
Opinion provided by Committee for Medicinal Products for Human Use
European Commission final decision
Vokanamet Article-20 procedure - Annex I - III (PDF/973.59 KB)
First published: 18/05/2016
Last updated: 18/05/2016
Invokana Article-20 procedure - Annex I - III (PDF/517.74 KB)
First published: 18/05/2016
Last updated: 18/05/2016
Jardiance Article-20 procedure - Annex I - III (PDF/347.79 KB)
First published: 18/05/2016
Last updated: 18/05/2016
SGLT2 inhibitors Article-20 procedure - Annex IV (PDF/44.81 KB)
First published: 18/05/2016
Last updated: 18/05/2016
Xigduo Article-20 procedure - Annex I - III (PDF/630.1 KB)
First published: 18/05/2016
Last updated: 18/05/2016
Forxiga Article-20 procedure - Annex I - III (PDF/503.21 KB)
First published: 18/05/2016
Last updated: 18/05/2016
Synjardy Article-20 procedure - Annex I - III (PDF/479.6 KB)
First published: 18/05/2016
Last updated: 18/05/2016
SGLT2 inhibitors Article-20 procedure - EMA confirms recommendations to minimise ketoacidosis risk with SGLT2 inhibitors for diabetes (PDF/92.15 KB)
First published: 26/02/2016
Last updated: 18/05/2016
EMA/142655/2016
Description of documents published
Please note that some of the listed documents apply only to certain procedures.
- Overview - lay-language summary of the stage of the procedure
- Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
- Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
- List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
- Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
- List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
- List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
- Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
- Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
- Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
- Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
- Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
- Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
- Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
- Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)
Note that older documents may have different titles.
News
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26/02/2016
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26/02/2016
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12/02/2016
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12/02/2016
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15/01/2016
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06/11/2015
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09/10/2015
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12/06/2015