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 and empagliflozin 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. |
Consideration should be given to prescribing the components of combination products as separate medicines perioperatively. Patients undergoing Bariatric Surgery
Patients with type 2 diabetes mellitus commencing liver reduction diet (LRD): Patients are at increased risk of electrolyte disturbances and volume depletion during this period; hence, SGLT2-Inhibitors should be discontinued as the LRD commences3 (see Further Information). Patients with type 2 diabetes mellitus not following a LRD: Follow the advice above for Elective Surgery Other Patients who require reduced calorie intake prior to their procedure (e.g, those 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. Patients undergoing Bariatric Surgery
Due to the nature of bariatric procedures, there is an increased risk of dehydration3 and overall improvement of glycaemic control due to weight loss. Discontinuation of SGLT-2 inhibitors should be considered after surgery. Blood glucose should be monitored until eating habits and food intake stabilises3. Patients should have their need for ongoing pharmacological management of their diabetes reviewed by their General Practitioner / Bariatric Surgical Team. For combination products containing metformin, please refer to individual monographs |
Hypotension
SGLT-2 inhibitors can increase the risk of hypotension when used concomitantly with the antiemetics droperidol and prochlorperazine2.
Iodinated Contrast Agents
Caution with combination products containing metformin and concomitant use of iodinated contrast agents4, 5, 6 – see Metformin monograph. Non-Steroidal Anti-inflammatory Drugs (NSAIDs)
Caution with combination products containing metformin and concomitant use of NSAIDs4, 5, 6– see Metformin monograph. |
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 inhibitor4, 5, 6, 7, 8, 9, 10, 11. 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 recommended4, 5, 6, 7, 8, 9, 10, 11. Temporary interruption of treatment with SGLT-2 inhibitors is recommended for patients who develop volume depletion until the depletion has been corrected4, 5, 6, 7, 8, 9, 10, 11. Lactic Acidosis
Risk of lactic acidosis with combination products containing metformin4, 5, 6– 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. Liver Reduction Diet (LRD)
Most people needing bariatric surgery have a large, fatty liver which can cause difficulty for laparoscopic surgery, as the stomach cannot be easily accessed. The LRD typically start 10 – 15 days prior to bariatric surgery and is based on low calories, in particular low carbohydrate, and fat. This forces stored glycogen to be released from the liver (plus some water), making it softer, more flexible and easier to move. Due to the reduced calorie and carbohydrate intake, CBG levels will most likely be reduced. In addition, weight loss itself stimulates ketone production and can increase the risk of euglycaemic DKA developing12. Therefore, SGLT-2 inhibitors should be discontinued at the start of the LRD. |
- 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]
- Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 28th February 2021]
- Mulla, CM, Baloch HM, & Hafida S. Management of Diabetes in Patients Undergoing Bariatric Surgery. Current Diabetes Reports (2019) 19:112
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Elasha H, Elsheikh AM, Wafa W, et al. SGLT2 Inhibition May Precipitate Euglycemic DKA after Bariatric Surgery. Clin Diabetes Res 2018, 2(1):40-42. DOI:10.36959/647/492
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