SGLT2 inhibitors

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision

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.


1PRAC recommendations issued on 11 February 2016

Key facts

About this medicine
Approved name
SGLT2 inhibitors
International non-proprietary name (INN) or common name
canagliflozin, dapagliflozin,empagliflozin
Associated names
  • Edistride
  • Ebymect
  • Xigduo
  • Vokanamet
  • Synjardy
  • Jardiance
  • Invokana
  • Forxiga
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-20/1419
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.

Decision making model
PRAC-CHMP-EC
Authorisation model
Centrally authorised product(s)
Key dates and outcomes
Procedure start date
11/06/2015
PRAC recommendation date
11/02/2016
CHMP opinion/CMDh position date
25/02/2016
EC decision date
28/04/2016
Outcome
Risk minimisation measures

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Opinion provided by Committee for Medicinal Products for Human Use

European Commission final decision

  • List item

    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

  • List item

    Vokanamet Article-20 procedure - Annex I - III (PDF/973.59 KB)


    First published: 18/05/2016
    Last updated: 18/05/2016

  • List item

    Invokana Article-20 procedure - Annex I - III (PDF/517.74 KB)


    First published: 18/05/2016
    Last updated: 18/05/2016

  • List item

    Jardiance Article-20 procedure - Annex I - III (PDF/347.79 KB)


    First published: 18/05/2016
    Last updated: 18/05/2016

  • List item

    SGLT2 inhibitors Article-20 procedure - Annex IV (PDF/44.81 KB)


    First published: 18/05/2016
    Last updated: 18/05/2016

  • List item

    Xigduo Article-20 procedure - Annex I - III (PDF/630.1 KB)


    First published: 18/05/2016
    Last updated: 18/05/2016

  • List item

    Forxiga Article-20 procedure - Annex I - III (PDF/503.21 KB)


    First published: 18/05/2016
    Last updated: 18/05/2016

  • List item

    Synjardy Article-20 procedure - Annex I - III (PDF/479.6 KB)


    First published: 18/05/2016
    Last updated: 18/05/2016

  • List item

    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

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or CMDh
    • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
    • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
    • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
    • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
    • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
    • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
    • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

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