Metformin and metformin-containing medicines

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

Overview

Use of metformin to treat diabetes now expanded to patients with moderately reduced kidney function

Recommendations for patients with kidney impairment updated in product information

On 13 October 2016, the European Medicines Agency (EMA) concluded that metformin-containing medicines can now be used in patients with moderately reduced kidney function (GFR [glomerular filtration rate] = 30–59 ml/min) for the treatment of type 2 diabetes. The product information for these medicines will be updated to revise the current contraindication and give information about doses, monitoring and precautions in patients with reduced kidney function.

The recommendations were the result of a review by EMA of metformin-containing medicines following concerns that current scientific evidence does not justify a contraindication in patients with moderate reduction of kidney function. The current product information also varies between countries and products in the EU and is no longer consistent with clinical guidelines.

Metformin may increase the risk of a rare but serious complication called lactic acidosis, which occurs when naturally produced lactic acid builds up in the blood faster than it can be removed. Currently, the product information states that metformin must not be used in patients with reduced kidney function because these patients are considered to be at a higher risk of developing lactic acidosis as their kidneys do not remove metformin efficiently enough.

However, after considering the scientific literature, clinical data, epidemiological studies and clinical guidelines from medical bodies, EMA concluded that the large patient population with moderately reduced kidney function can benefit from use of metformin. Clear dosing recommendations and monitoring before and during treatment aim to minimise any possible increased risk in these patients. The contraindication for patients with severely reduced kidney function will remain (GFR less than 30 ml/min).

Companies marketing metformin-containing medicines will be requested to closely monitor and analyse future lactic acidosis cases and report these during upcoming periodic safety reviews in order to follow up on any changes in the frequency of this side effect. The product information for metformin- containing medicines will be updated to reflect the new recommendations and to ensure that the same advice is given to all patients in the EU.

Key facts

About this medicine
Approved name
Metformin and metformin-containing medicines
International non-proprietary name (INN) or common name
metformin
Associated names
  • Xigduo
  • Vipdomet
  • Velmetia
  • Synjardy
  • Ristfor
  • Komboglyze
  • Jentadueto
  • Janumet
  • Icandra (previously Vildagliptin / metformin hydrochloride Novartis)
  • Glubrava
  • Eucreas
  • Efficib
  • Ebymect
  • Competact
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-31/1432
Type
Article 31 referrals

This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

Key dates and outcomes
CHMP opinion date
13/10/2016
EC decision date
12/12/2016

All documents

Procedure started

Opinion provided by Committee for Medicinal Products for Human Use

  • List item

    Metformin Article-31 referral - Use of metformin to treat diabetes now expanded to patients with moderately reduced kidney function (PDF/94.06 KB)


    First published: 14/10/2016
    Last updated: 21/12/2016
    EMA/603690/2016

  • List item

    Metformin Article-31 referral - CHMP assessment report (PDF/568.79 KB)


    First published: 21/12/2016
    Last updated: 21/12/2016
    EMA/867221/2016

  • List item

    Metformin Article-31 referral - Annex II (PDF/28.38 KB)


    First published: 21/12/2016
    Last updated: 21/12/2016

  • List item

    Metformin Article-31 referral - Annex III (PDF/63.94 KB)


    First published: 21/12/2016
    Last updated: 21/12/2016

  • List item

    Metformin Article-31 referral - Changes to product information (PDF/57.33 KB)


    First published: 14/10/2016
    Last updated: 14/10/2016

  • List item

    Metformin Article-31 referral - Annex I (PDF/477.34 KB)


    First published: 03/02/2016
    Last updated: 21/12/2016
    EMA/82128/2016

  • 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.

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