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


 

Canagliflozin, Dapagliflozin, Empagliflozin, Ertugliflozin


  Issues for Surgery


Increased risk of post-operative infection and delayed wound healing due to poor glycaemic control 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

SGLT-2 inhibitors should be taken as normal the day prior to 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).

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

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 and VRIII (where applicable) has been stopped1 (see Further Information).


  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 agents5, 6, 7 – see Metformin monograph.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

Caution with combination products containing metformin and concomitant use of NSAIDs5, 6, 7 – see Metformin monograph.


  Further Information


MHRA/CHM Advice (Updated April 2016) – Risk of DKA with SGLT-2 Inhibitors

Serious, life-threatening, and fatal cases of DKA have been reported rarely in patients taking an SGLT-2 inhibitor3, 4, 5, 6, 7, 8. 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)
  • Do not restart treatment following major surgery until 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. 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.

Lactic Acidosis

Risk of lactic acidosis with combination products containing metformin5, 6, 7 – 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. Patients expected to miss more than one meal should have VRIII1.

 

  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 30th March 2019]
  2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 30th March 2019]
  3. Summary of Product Characteristics – Forxiga® (dapagliflozin) 10mg film-coated tablets. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 06/04/2019 [date of revision of the text April 2019]
  4. Dapagliflozin. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 30th March 2019]
  5. Summary of Product Characteristics – Xigduo® (dapagliflozin + metformin) 5mg/1,000mg film coated tablets. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 06/04/2019 [date of revision of the text March 2019]
  6. Summary of Product Characteristics – Vokanamet® (canagliflozin + metformin) 50mg/1,000mg film-coated tablets. Napp Pharmceuticals Limited. Accessed via www.medicines.org.uk 09/04/2019 [date of revision of the text March 2019]
  7. Summary of Product Characteristics – Synjardy® (empagliflozin + metformin) film coated tablets. Boehringer Ingelheim Limited. Accessed via www.medicines.org.uk 09/04/2019 [date of revision of the text January 2019]
  8. Summary of Product Characteristics – Steglatro® (ertugliflozin) Film-Coated Tablets. Merck Sharp & Dohme Limited. Accessed via www.medicines.org.uk 08/06/2019 [date of revision of the text April 2019]