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


 

Dulaglutide, Exenatide, Liraglutide, Lixisenatide, Semaglutide


  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 surgery (including any combination products)1.

Morning or Afternoon Surgery
Continue.

EXCEPT: 

  • Xultophy®– contains liraglutide + insulin degludec (See Insulin monograph)
  • Suliqua® – contains lixisenatide + insulin glargine (See Insulin monograph)

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 continue GLP-1 receptor agonist1, 2.

Ensure emergency treatment of hypoglycaemia is prescribed i.e. Glucogel® and 20% dextrose. Rapid acting insulin should also be prescribed1, 2.

Post-operative Advice

Continue, even if VRIII is used.

NB: For GLP-1 analogues 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.


  Interaction(s) with Common Anaesthetic Agents


None2, 3, 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 phase 3, 4, 8, 9, 11, 12, 13, 14.

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 injection4, 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 injection4, 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 analogues. 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 depletion3, 4, 5, 6, 7, 8, 9, 10.

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.

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 discontinuation15.

 

  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 24th March 2019]
  2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 24th March 2019]
  3. 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 24/03/2019 [date of revision of the text March 2019]
  4. Summary of Product Characteristics – Byetta® (exenatide) 5 micrograms solution for injection. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 24/03/2019 [date of revision of the text August 2017]
  5. Summary of Product Characteristics – Bydureon® (exenatide) 2mg powder and solvent for prolonged-release suspension for injection in pre-filled pen. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 24/03/2019 [date of revision of the text February 2019]
  6. 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 24/03/2019 [date of revision of the text August 2017]
  7. Summary of Product Characteristics – Xultophy® (100units/ml insulin degludec + 3.6 mg/ml liraglutide) solution for injection in a pre-filled pen.
  8. Novo Nordisk Limited. Accessed via www.medicines.org.uk 24/03/2019 [date of revision of the text October 2018]
  9. Summary of Product Characteristics – Lyxumia ® (lixisenatide) 10 micrograms solution for injection. SANOFI. Accessed via www.medicines.org.uk 24/03/2019 [date of revision of the text September 2017]
  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 24/03/2019 [date of revision of the text February 2019]
  11. Summary of Product Characteristics – Ozempic® (semaglutide) 0.25mg, 0.5mg and 1mg solution for injection in pre-filled pen. Novo Nordisk Limited. Accessed via www.medicines.org.uk 30/03/2019 [date of revision of the text December 2018]
  12. Dulaglutide. 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]
  13. Exenatide. 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]
  14. Liraglutide. 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]
  15. National Institute for Health and Care Excellence. Obese, overweight with risk factors: liraglutide (Saxenda). Evidence Summary (ES14), Published June 2017. www.nice.org.uk/guidance/es14 [Accessed 30th March 2019]