Sodium-glucose co-transporter-2 (SGLT-2) InhibitorsGLT-2 inhibitors (gliflozins)


 

Canagliflozin, Dapagliflozin, Empagliflozin, Ertugliflozin


  Issues for Surgery


For type 2 diabetes – increased risk of post-operative infection and delayed wound healing due to poor glycaemic control if omitted.

For treatment of heart failure (dapagliflozin only) – potential exacerbation of symptoms if omitted.

Risk of diabetic ketoacidosis (DKA) if continued (see Further Information).

Risk of volume depletion, hypotension and / or electrolyte disturbances if continued (see Further Information).

Combination products containing Metformin – risk of lactic acidosis if continued (see Interaction(s) with other Common Medicines used in the Perioperative Period and Further Information)

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


  Advice in the Perioperative period


Elective and Emergency Surgery

Omit on day before surgery (including combination products)1.

Morning or Afternoon Surgery
Omit on day of surgery1.

Combination Products: -

  • Vokanamet® – contains canagliflozin + metformin
  • Xigduo® – contains dapagliflozin + metformin
  • Synjardy® – contains empagliflozin + metformin

  • Qtern® – contains dapagliflozin + saxagliptin (see Dipeptidylpeptidase-4 (DPP-IV) Inhibitors monograph but follow advice for SGLT-2 inhibitors).
  • Glyxambi® - contains empagliflozin + linagliptin (see also Dipeptidylpeptidase-4 (DPP-IV) Inhibitors monograph but follow advice for SGLT-2 inhibitors).

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

Patients required to follow a reduced calorie diet prior to surgery (e.g. Bariatric surgery or patients who require pre-operative bowel preparation)

Restricted food intake is a risk factor for DKA in patients taking an SGLT-2 inhibitor.  A longer period of treatment cessation may be necessary and, in general, should coincide with reduced food intake.  Trusts / Health Boards should ensure they have clear guidance in place for these patients so that they can be appropriately managed1.

Emergency Surgery

Withhold SGLT-2 inhibitors on admission to hospital1, 2.  Monitor capillary blood glucose (CBG) levels closely and treat any hypoglycaemia accordingly.  Check ketones (preferably blood not urine) daily1.

Perioperative Considerations

Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated (see Further Information) and omit SGLT-2 inhibitor 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

DO NOT restart until eating and drinking normally, any volume depletion has been corrected, VRIII (where applicable) has been stopped, ketone levels are normal and patient is medically stable1, 2 (see Further Information). Once restarted check ketones (preferably blood not urine) daily whilst an inpatient, even if CBG is normal1..


  Interaction(s) with Common Anaesthetic Agents


Hypotension

SGLT-2 inhibitors 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


Hypotension

SGLT-2 inhibitors can increase the risk of hypotension when used concomitantly with the antiemetics droperidol and prochlorperazine 2.

Iodinated Contrast Agents

Caution with combination products containing metformin and concomitant use of iodinated contrast agents3, 4, 5 – see Metformin monograph.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

Caution with combination products containing metformin and concomitant use of NSAIDs3, 4, 5– see Metformin monograph.


  Further Information


MHRA / CHM Advice (Updated April 2016) – Risk of DKA with SGLT-2 Inhibitors and (March 2020) – SGLT-2 Inhibitors: monitor ketones in blood during treatment interruption for surgical procedures

Serious, life-threatening, and fatal cases of DKA have been reported rarely in patients taking an SGLT-2 inhibitor3, 4, 5, 6, 7, 8, 9, 10. The presentation can be atypical, with patients having only moderately elevated blood glucose levels. Patients undergoing surgery may be at higher risk of DKA. The following European Medicines Agency (EMA) advice should be followed during the perioperative period2: -

  • Test for raised ketones in patients with signs and symptoms of DKA, even if plasma glucose levels are near-normal
  • Discontinue treatment if DKA is suspected or diagnosed – do not restart unless another cause for DKA is identified and resolved (seek advice from specialist diabetes team)
  • Monitor ketone levels during SGLT-2 inhibitor treatment interruption in patients who have been hospitalised for major surgery – measurement of blood ketones is preferred to urine
  • Do not restart treatment following major surgery until ketone levels are normal and the patient’s condition has stabilised

Volume depletion, hypotension and/or electrolyte imbalances

SGLT-2 inhibitors increase diuresis associated with a modest decrease in blood pressure, which may be more pronounced in patients with very high blood glucose concentrations. For patients receiving SGLT-2 inhibitors where there is risk of volume depletion (i.e. during surgery), careful monitoring of volume status and electrolytes is recommended3, 4, 5, 6, 7, 8, 9, 10. Temporary interruption of treatment with SGLT-2 inhibitors is recommended for patients who develop volume depletion until the depletion has been corrected3, 4, 5, 6, 7, 8, 9, 10.

Lactic Acidosis

Risk of lactic acidosis with combination products containing metformin3, 4, 5– see Metformin 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.

 

  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 – Xigduo® (dapagliflozin + metformin) 5mg/1,000mg film coated tablets. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text November 2019]
  4. Summary of Product Characteristics – Vokanamet® (canagliflozin + metformin) 50mg/1000mg film-coated tablets. Napp Pharmaceuticals Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text May 2020]
  5. Summary of Product Characteristics – Synjardy® (empagliflozin + metformin) 5mg/1,000mgfilm-coated tablets. Boehringer Ingelheim Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text January 2019]
  6. Summary of Product Characteristics – Forxiga® (dapagliflozin) 10mg film-coated tablets. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text January 2021]
  7. Dapagliflozin. 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]
  8. Summary of Product Characteristics – Steglatro® (ertugliflozin) 5mg Film-Coated Tablets. Merck Sharp & Dohme (UK) Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text July 2020]
  9. Summary of Product Characteristics – Invokana® (canagliflozin) 100mg film-coated tablets. Napp Pharmaceuticals Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text June 2020]
  10. Summary of Product Characteristics – Jardiance® (empagliflozin) 10mg film-coated tablets. Boehringer Ingelheim Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text September 2020]