UK Clinical Pharmacy Association

Liraglutide

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 – see Further information.

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

Potential risk of aspiration and post-operative nausea and vomiting (PONV) if continued (see Further information).

Delay in absorption of some medicines due to delay in gastric emptying if continued (see Interactions with other 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 product Xultophy®).

Advice in the perioperative period

Elective and emergency surgery 

Continue.

Except:

  • Xultophy®– contains liraglutide + insulin degludec (follow advice in Long-acting insulin drug record)
  • Patients undergoing surgery that requires liver reduction diet (LRD) – see below.
  • Patients without diabetes mellitus taking liraglutide for weight management (see Perioperative considerations and Further information) - discuss with anaesthetist.

Patients undergoing surgery that requires liver reduction diet (LRD) (e.g. bariatric surgery, gallbladder surgery)

For patients with type 2 diabetes mellitus commencing liver reduction diet (LRD), consideration should be given to stopping liraglutide when the LRD commences, with close monitoring of capillary blood glucose (CBG) (see Further information). 

For patients with type 2 diabetes mellitus not following an LRD, follow the advice above for elective and emergency surgery.

For combination product containing insulin degludec – follow advice in long-acting insulin drug record.

Perioperative considerations

Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated (see Further information) and continue liraglutide.

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

Risk of aspiration

An individualised risk assessment should take place for patients taking liraglutide perioperatively to manage the potential risk of aspiration. Consideration should be given to any risk factors for aspiration, including concurrent diabetic gastroparesis. Precautions that can be used to reduce the risk include regional anaesthesia; tracheal intubation; modified rapid sequence induction and intubation; ramped position; awake extubation; and pre-operative gastric ultrasound, when available. A shared decision-making approach should be taken around the risks and benefits of continuing and stopping the medication, including potential alternatives (see Further information).

Post-operative advice

Continue, even if VRIII is used.

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 liraglutide should be considered post-operatively. Blood glucose should be monitored until eating habits and food intake stabilises. Patients should have their need for ongoing pharmacological management of their diabetes reviewed by their GP or bariatric surgical team.

Combination products containing insulin degludec – follow advice in long-acting insulin drug record.

Interactions with common anaesthetic agents

None.

Interactions with other common medicines used in the perioperative period

Gastric emptying

Liraglutide 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.

Further information

Risk of aspiration and post-operative nausea and vomiting (PONV)

Two perioperative randomised controlled trials have found that nausea and vomiting was associated with newly commenced GLP-1 receptor agonists. It is unknown whether patients on long-term treatment experience the same adverse effects, although gastrointestinal side-effects do diminish over time.

The American Society of Anesthesiologists (ASA) published a consensus-based recommendation that GLP-1 receptor agonists be stopped prior to surgery due to isolated case reports of aspiration. The evidence on which this recommendation is based is limited and no other organisation or regulatory body has followed with similar recommendations. The advice could potentially lead to deterioration in perioperative glycaemic control and associated complications, such as infection, acute kidney injury (AKI), acute coronary syndromes (ACS), cerebrovascular events, and death.

Where GLP-1 receptor agonists are stopped pre-operatively it may be necessary to ‘bridge’ with insulin therapy. However, this comes with its own risks in terms of hypoglycaemia, potential medication errors, and inferior glycaemic control.

Furthermore, if more than 2 doses are missed, there may be a need for gradual reintroduction post-operatively to avoid common side-effects associated with initiation/reinitiation, such as nausea and diarrhoea. This may further impact on glycaemic control.

Due to the current lack of robust evidence to support the association of the increased risk of aspiration under anaesthesia with GLP-1 receptor agonists, and the concerns outlined above the Centre for Perioperative Care have reconfirmed their position to continue perioperatively for patients with diabetes mellitus.

NB: liraglutide for weight management is outside the scope of CPOC guidance. It is recommended that there is a shared decision-making process that occurs with the patient to determine the risks and benefits of continuing or stopping liraglutide when being used for this indication in the perioperative period (see Perioperative considerations).

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 depletion.

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)). 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).

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. There is no clear evidence to confirm if and how long the benefits of liraglutide will persist after treatment discontinuation.

Liver reduction diet (LRD)

Patients with a high BMI often have a large, fatty liver which can cause difficulty for laparoscopic surgery, as the stomach cannot be easily accessed. The LRD typically starts 10 – 15 days prior to 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

Centre for Perioperative Care. Guideline for Perioperative Care for People with Diabetes Mellitus Undergoing Elective and Emergency Surgery (updated October 2023). Available at: https://cpoc.org.uk/guidelines-resources/guidelines [Accessed on 12th February 2024]

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

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 12th February 2024]

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 12/02/2024 [date of revision of the text October 2023]

Summary of Product Characteristics – Xultophy® (100 units/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 12/02/2024 [date of revision of the text October 2023]

Liraglutide. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http:www.medicinescomplete.com [Accessed 12th February 2024]

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 12th February 2024]

Dhatariya K, Levy N, Russon K et al. Perioperative use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors for diabetes mellitus. BJA 2024 DOI: 10.1016/j.bja.2023.12.015 

Summary of Product Characteristics – Saxenda® (liraglutide) 6 mg/ml solution for injection in a pre-filled pen. Novo Nordisk Limited. Accessed via www.medicines.org.uk 12/02/2024 [date of revision of the text October 2023]