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Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists

 

Dulaglutide, Exenatide, Liraglutide, Lixisenatide, Semaglutide

Following the press release from the American Society of Anesthesiologists on 29th June 2023 regarding the potential effects of GLP-1 Receptor Agonists on gastric emptying, this monograph is currently under review

  Issues for Surgery


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

For weight management (liraglutide only) – see Further Information.

Dehydration (including renal impairment/acute renal failure) if continued (see Further Information).

Delay in absorption of some medicines due to delay in gastric emptying if continued (see Interaction with Common Medicines used in the Perioperative Period).

Potential for hypoglycaemia when used in combination with a sulfonylurea or insulin and continued during nil by mouth (NBM) period (includes the combination products Xultrophy® and Suliqua®).

  Advice in the Perioperative period


Emergency or Elective Surgery
GLP-1 receptor agonists should be taken as normal the day prior to surgery1.

EXCEPT:

  • Suliqua® – contains lixisenatide + insulin glargine (See Long-acting Insulin monograph)
  • Xultophy®– contains liraglutide + insulin degludec (See Long-acting Insulin monograph)
  • Patients undergoing Bariatric Surgery – see below

Morning or Afternoon Surgery
Continue.

EXCEPT: 

  • Xultophy®– contains liraglutide + insulin degludec (See Long-acting Insulin monograph)
  • Suliqua® – contains lixisenatide + insulin glargine (See Long-acting Insulin monograph)
  • Patients undergoing Bariatric Surgery – see below

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): Consideration should be given to stopping GLP-1 receptor agonists when the LRD commences, with close monitoring of capillary blood glucose (CBG)2 (see Further Information). 

Patients with type 2 diabetes mellitus not following a LRD: Follow the advice above for Elective or Emergency Surgery.

For combination products containing Insulin – follow advice in Long-acting Insulin monograph.  

Perioperative Considerations
Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated (see Further Information) and continue GLP-1 receptor agonist1, 3.

Ensure emergency treatment of hypoglycaemia is prescribed i.e. Glucogel® and 20% dextrose. Rapid acting insulin should also be prescribed1, 3.

Post-operative Advice
Continue, even if VRIII is used.

NB: For GLP-1 receptor agonists that are administered on a weekly basis – where the usual day of administration is missed, consult product literature for advice on when to safely administer a dose.

Patients undergoing Bariatric Surgery
Improved glycaemic control is expected because of reduced calorie intake, early satiety and weight loss following bariatric surgery, therefore discontinuation of GLP-1 receptor agonists should be considered post-operatively2. Blood glucose should be monitored until eating habits and food intake stabilises2. Patients should have their need for ongoing pharmacological management of their diabetes reviewed by their General Practitioner / Bariatric Surgical Team.

Combination products containing insulin – follow advice in Long-acting Insulin Monograph.

  Interaction(s) with Common Anaesthetic Agents


None3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

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


Gastric Emptying
Dulaglutide, immediate release exenatide, liraglutide and lixisenatide may delay gastric emptying and have the potential to impact the rate of absorption of concomitantly administered oral medicinal products. Care should be taken in patients who may require oral medicinal products that require rapid gastrointestinal absorption during the perioperative phase4, 5, 9, 10, 12, 13, 14, 15.

Immediate-Release Exenatide and Lixisenatide
Oral medications that are particularly dependent on threshold concentrations for efficacy (e.g. antibiotics) should be taken 1 hour before immediate-release exenatide or lixisenatide injection5, 9.

Gastroresistant formulations containing substances sensitive for degradation in the stomach (e.g. proton pump inhibitors) should be taken 1 hour before or 4 hours after immediate-release exenatide or lixisenatide injection5, 9.

  Further Information


Dehydration
Signs and symptoms of dehydration, including renal impairment and acute renal failure, have been reported in patients treated with GLP-1 receptor agonists. Consideration should be given to the potential risk of dehydration in the perioperative period in relation to gastrointestinal side effects (i.e. vomiting) and precautions taken to avoid fluid depletion4, 5, 6, 7, 8, 9, 10, 11, 15.

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 (capillary blood glucose (CBG) >12mmol/L)1.

Weight Management
Liraglutide as Saxenda® is indicated as an adjunct in weight management. Whilst omission over a short-term period should not cause an issue, ability to sustain any weight loss achieved during treatment is unlikely if Saxenda® is stopped for any prolonged period of time. There is no clear evidence to confirm if and how long the benefits of liraglutide will persist after treatment discontinuation16.

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. Whilst GLP-1 receptor agonists do not cause hypoglycaemia, the reduction in dietary intake means they are unlikely to have any benefit.

  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. Busetto L, Dicker D, Azran C et al. Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management. Obesity Facts 2017;10:597 – 632. DOI: 10.1159/000481825
  3. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 28th February 2021]
  4. Summary of Product Characteristics – Trulicity® (dulaglutide) 0.75 mg solution for injection in pre-filled pen. Eli Lilly and Company Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text November 2020]
  5. Summary of Product Characteristics – Byetta® (exenatide) 5 micrograms solution for injection, prefilled pen. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text January 2021]
  6. Summary of Product Characteristics – Bydureon® (exenatide) 2mg prolonged-release suspension for injection in pre-filled pen (BCise). AstraZeneca UK Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text January 2021]
  7. Summary of Product Characteristics – Victoza® (liraglutide) 6 mg/ml solution for injection in pre-filled pen. Novo Nordisk Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text September 2020]
  8. Summary of Product Characteristics – Xultophy® (100units/ml insulin degludec + 3.6 mg/ml liraglutide) solution for injection in a pre-filled pen. Novo Nordisk Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text September 2020]
  9. Summary of Product Characteristics – Lyxumia ® (lixisenatide) 10 micrograms solution for injection. SANOFI. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text December 2020]
  10. Summary of Product Characteristics – Suliqua® (lixisenatide + insulin glargine) 100 units/ml + 33 micrograms/ml solution for injection in a pre-filled pen. SANOFI. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text August 2020]
  11. Summary of Product Characteristics – Ozempic® (semaglutide) 0.25mgsolution for injection in pre-filled pen. Novo Nordisk Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text December 2020]
  12. Dulaglutide. 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]
  13. Exenatide. 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]
  14. Liraglutide. 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]
  15. Summary of Product Characteristics – Rybelsus® (semaglutide). Novo Nordisk Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text November 2020]
  16. National Institute for Health and Care Excellence. Liraglutide for managing overweight and obesity. Technology Appraisal (TA664), Published December 2020. http://www.nice.org.uk/guidance/ta664 [Accessed 28th February 2021]
Dulaglutide Exenatide Liraglutide Lixisenatide Semaglutide