Metformin


  Issues for Surgery


For patients with diabetes – increased risk of post-operative infection and delayed wound healing due to poor glycaemic control if omitted.

Risk of lactic acidosis if continued (see Further Information).

Potential for hypoglycaemia when taken concomitantly with other blood glucose lowering medicines and continued during nil by mouth period.


  Advice in the Perioperative period


Elective Surgery

Metformin should be taken as normal the day prior to surgery (including any combination products)1.

Morning or Afternoon Surgery

If eGFR > 60 ml/min/1.73m2: -

  • Once or Twice daily dosing: Continue1, 2
  • Three times daily dosing: Omit lunchtime dose on day of surgery1, 2


If eGFR < 60 ml/min/1.73m2: -

  • Contrast media: Omit on the day of the surgery and for 48 hours post-operatively1, 2
  • No contrast media: Follow advice above for eGFR > 60 ml/min/1.73m2

This advice should also be followed for: -

  • Combination products containing metformin – but also see Sodium Glucose Co-transporter 2 Inhibitors (SGLT-2) monograph for important information regarding combination products containing canagliflozin (Vokanamet®), dapagliflozin (Xigduo®) and empagliflozin (Synjardy®)
  • Modified release (MR/SR) preparations of metformin
  • Patients taking metformin for Polycystic Ovary Syndrome (PCOS)

Consideration should be given to prescribing the components of combination products as separate medicines perioperatively.

Emergency Surgery 

In the event of emergency surgery and the patient has already taken their metformin dose(s). Monitor blood glucose levels closely and treat any hypoglycaemia accordingly.

Perioperative Considerations

Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated (see Further Information) and omit metformin during VRIII treatment1.

 Ensure emergency treatment of hypoglycaemia is prescribed i.e. Glucogel® and 20% dextrose. Rapid acting insulin should also be prescribed1, 2.

Post-operative Advice

Check renal function post-operatively; once eating and drinking normally and VRIII (where applicable) has been stopped1 follow the advice below:-

  • eGFR > 60ml/min/1.73m(with or without use of contrast media) – restart metformin
  • eGFR 30 – 60ml/min/1.73mand no use of contrast media – restart metformin (BUT ensure that the dose is not increased above the patient’s usual pre-operative dose)
  • eGFR 30 – 60ml/min/1.73m2 and use of contrast media – do not restart metformin until 48 hours post-operatively.
  • eGFR < 30ml/min/1.73m(with or without use of contrast media) – do not restart metformin until renal function is stabilised. Seek advice from Diabetes Specialist Team


  Interaction(s) with Common Anaesthetic Agents


None2, 3, 4, 5.


  Interaction(s) with other Common Medicines used in the Perioperative Period


Iodinated Contrast Agents

Iodinated contrast agents can cause contrast-induced nephropathy (CIN). If CIN occurs, this can result in metformin accumulation and increased risk of lactic acidosis, although there is a lack of any valid evidence3, 4, 5, 6. Ensure that renal function is checked prior to administration of iodinated contrast agents.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

Care with concomitant use of NSAIDs due to risk of impaired renal function and subsequent increased risk of lactic acidosis2, 3, 4, 5.


  Further Information


Lactic Acidosis

Lactic acidosis is a very rare but serious metabolic complication, which most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs as renal function deteriorates and increases the risk of lactic acidosis. Other risk factors include dehydration and prolonged fasting2, 3, 4.

It should be noted that most manufacturers advise that metformin / metformin-containing products should be discontinued for all patients at the time of surgery under general, spinal or epidural anaesthesia, including those patient receiving iodinated contrast agents; and restarted no earlier than 48 hours after on resumption of oral nutrition and where renal function has been checked and is stable3, 4, 5. However, current national guidance does not support this general restriction in patients with an eGFR > 60ml/min/1.73mand the advice above should be followed1, 6.

VRIII

Patients with a planned short starvation period (no more than one missed meal in total) should be managed by modification of their usual diabetes medication, avoiding VRIII wherever possible. Patients expected to miss more than one meal should have VRIII1.

NB: patients on ONCE DAILY metformin, should only start VRIII if their capillary blood glucose levels are > 12mmol/L on 2 consecutive occasions1.

Use of VRIII is not indicated for patients taking metformin for PCOS.

 

  References


  1. Joint British Diabetes Societies for Inpatient Care. Management of adults with diabetes undergoing surgery and elective procedures: improving standards (Revised March 2016). Available at: www.diabetes.org.uk [Accessed 5th April 2019]
  2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 4th April 2019]
  3. Summary of Product Characteristics – Glucophage® (metformin) 500mg film coated tablets. Merck. Accessed via www.medicines.org.uk 05/04/2019 [date of revision of the text January 2017]
  4. Summary of Product Characteristics – Glucophage® SR (metformin) 500mg, 750mg and 1000mg prolonged release tablets. Merck. Accessed via www.medicines.org.uk 05/04/2019 [date of revision of the text May 2017]
  5. Metformin. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 5th April 2019]
  6. The Royal College of Radiologists. Standards for intravascular contrast administration to adult patients, Third edition. London: The Royal College of Radiologists; 2015. www.rcr.ac.uk [Accessed 5th April 2019]