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.

Combination products containing Canagliflozin, Dapagliflozin or Empagliflozin – risk of diabetic ketoacidosis (DKA), volume depletion, hypotension and / or electrolyte disturbances if continued (see Further Information).

  Advice in the Perioperative period


Elective Surgery

Metformin should be taken as normal the day prior to surgery1.

EXCEPT:

  • Combination products containing canagliflozin (Vokanamet®), dapagliflozin (Xigduo®) or empagliflozin (Synjardy®) – see Sodium Glucose Co-transporter 2 (SGLT-2) monograph)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 pioglitazone (Competact®) – but also see Pioglitazone monograph
  • Combination products containing alogliptin (Vipdomet®), linagliptin (Jentadueto®), saxagliptin (Komboglyze®), sitagliptin (Janumet®) or vildagliptin (Eucreas®) – but also see Dipeptidylpeptidase-4 (DPP-IV) Inhibitors monograph
  • Modified release (MR/SR) preparations of metformin
  • Patients taking metformin for Polycystic Ovary Syndrome (PCOS)

For combination products containing canagliflozin (Vokanamet®), dapagliflozin (Xigduo®) or empagliflozin (Synjardy®) - see Sodium Glucose Co-transporter 2 (SGLT-2) monograph).

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 capillary blood glucose (CBG) 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

Combination Products

Follow advice above for restarting combination products containing pioglitazone or DPP-IV inhibitors.

Combination products containing SGLT-2 inhibitors should not be restarted until patient eating and drinking normally and patient’s condition is stable (see Sodium Glucose Co-transporter 2 Inhibitors (SGLT-2) monograph).

  Interaction(s) with Common Anaesthetic Agents


None for products containing metformin alone2, 3, 4, 5.

Hypotension 

Combination products containing a SGLT-2 inhibitor can increase the risk of hypotension when used concomitantly with inhalational or intravenous anaesthetics2.


  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.

Hypotension

Combination products containing a SGLT-2 inhibitor can increase the risk of hypotension when used concomitantly with the antiemetics droperidol and prochlorperazine2.


  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.

DKA, Volume Depletion, Hypotension and / or Electrolyte Imbalance

Risk of DKA, volume depletion, hypotension and / or electrolyte imbalance with combination product containing canagliflozin, dapagliflozin or empagliflozin – see Sodium Glucose Co-transporter 2 (SGLT-2) Inhibitors monograph.

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 (although VRIII may be necessary if emergency surgery or in people with poorly controlled diabetes (HbA1c >69mmol/mol))1. Patients with type 2 diabetes who are expected to miss more than one meal should have VRIII if they develop hyperglycaemia (CBG >12mmol/L)1.

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

 

  References


  1. Centre for Perioperative Care. Guideline for Perioperative Care for People with Diabetes Mellitus Undergoing Elective and Emergency Surgery (March 2021). Available at: https://cpoc.org.uk/guidelines-resources/guidelines [Accessed on 8th March 2021]
  2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 28th February 2021]
  3. Summary of Product Characteristics – Glucophage® (metformin) 500mg film coated tablets. Merck. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text August 2019]
  4. Summary of Product Characteristics – Glucophage® SR (metformin) 1000mg prolonged release tablets. Merck. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text December 2020]
  5. Biguanide Antidiabetics. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. Electronic version. Truven Health Analytics, Greenwood Village, Colorado, USA. http://www.micromedexsolutions.com [Accessed 1st March 2021]
  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 28th February 2021]