Brands of this drug
Tresiba®
Combination product: Xultophy®
Issues for surgery
Increased risk of post-operative infection and delayed wound healing due to poor glycaemic control if omitted.
Hypoglycaemia if continued during nil by mouth period / during liver reduction diet (LRD) in patients undergoing bariatric surgery.
For Xultophy® – dehydration (including renal impairment / acute renal failure) if continued (see Liraglutide monograph)
For Xultophy®– potential risk of aspiration and post-operative nausea and vomiting (PONV) if continued (see Liraglutide monograph)
For Xultophy® – delay in absorption of some medicines due to delay in gastric emptying if continued (see Liraglutide monograph)
Advice in the perioperative period
Insulin products are classified according to their duration of action, and it is important to understand the type of insulin the patient is on in relation to the advice to be given perioperatively. Confirm with the patient the exact name, strength, dose, frequency, and preparation of insulin(s) that they are using (see Further information).
Elective surgery
Adjust doses whilst not eating (including combination products) – see table below.
Except: Patients undertaking a liver reduction diet pre-operatively – see Patients undergoing surgery that requires liver reduction diet (LRD).
Combination product:
- Xultophy® (insulin degludec with liraglutide) – follow advice in table below but also see Liraglutide drug record.
When reducing insulin doses round to the nearest whole unit. The dose of Xultophy® is expressed in terms of ‘dose steps’ (where 10 dose steps refers to 10 units of insulin).
If district nursing or care home staff usually administer the insulin, consider practical implications of adjusting doses (see Further information).
Consideration should be given to prescribing the components of combination products as separate medicines perioperatively.
NB: The advice is also the same regardless of whether insulin degludec is being used as part of a basal-bolus regimen in type 1 diabetes mellitus or monotherapy / add-on therapy for type 2 diabetes mellitus.
| Regimen | Day before procedure* | Day of procedure* |
|---|---|---|
| Once daily (in the morning) | No dose change | Take 80% of usual dose |
| Once daily(at lunchtime) | Take 80% of usual dose | Check CBG on admission |
| Once daily(at evening) | Take 80% of usual dose | Check CBG on admission |
| Twice daily | Take morning dose as usual and taken 80% of usual evening dose | Take 80% of morning dose |
Patients undergoing surgery that requires liver reduction diet (LRD)
Patients with type 1 diabetes mellitus
An individualised management plan should be formulated with the diabetes specialist team.
Patients with type 2 diabetes mellitus
Give 50% of usual dose of insulin degludec when the LRD commences, with close monitoring of CBG (see Further information).
When reducing insulin doses round to the nearest whole unit.
Emergency surgery
Monitor CBG, ketones, renal profile, and lactate on admission to exclude diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS). The advice given above can be applied to patients presenting for emergency surgery; however, it must be remembered that these patients are high risk and are likely to require intravenous insulin infusion; either variable rate intravenous insulin infusion (VRIII), or in the case of DKA or HHS a fixed rate intravenous insulin infusion – see Further information. Continue to monitor ketones if CBG greater than 13mmol/mol.
Perioperative considerations
Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated, with the patient’s insulin degludec continued at 80% of their usual pre-operative dose (see above and Further information).
Ensure emergency treatment of hypoglycaemia is prescribed, i.e. Glucogel® and 20% dextrose. Rapid-acting insulin should also be prescribed.
Risk of aspiration (for Xultophy®)
See advice in Liraglutide monograph regarding need for individualised risk assessment to manage potential risk of aspiration.
Post-operative advice
Encourage an early return to normal eating and drinking (as deemed appropriate by the surgical team), facilitating return to the patient’s usual insulin regimen. However, the insulin dose(s) may need adjusting, as insulin requirements can change due to post-operative stress, infection or altered food intake – monitor CBG levels and seek advice from specialist diabetes team if necessary.
Patients undergoing bariatric surgery
Improved glycaemic control is expected because of reduced calorie intake, early satiety and weight loss following bariatric surgery.
Patients with type 1 diabetes mellitus
REview by the specialist diabetes team post-operatively.
Patients with type 2 diabetes mellitus
Discontinue insulin degludec post-operatively. Blood glucose should be monitored until eating habits and food intake stabilises. If there is a need to recommence insulin degludec post-operatively the dose should be tapered on discharge with strict glucose monitoring to avoid hypoglycaemia. Patients should have their need for ongoing pharmacological management of their diabetes reviewed by their general practitioner or bariatric surgical team.
Interactions with common anaesthetic agents
Reduction of blood-glucose lowering effect
Substances that may reduce the blood-glucose-lowering effect include sympathomimetics (e.g. epinephrine / adrenaline).
Interactions with other common medicines used in the perioperative period
Enhancement of blood-glucose lowering effect
Substances that may enhance the blood-glucose lowering effect of insulin and increase susceptibility to hypoglycaemia include sulphonamide antibiotics (e.g. co-trimoxazole).
Reduction of blood-glucose lowering effect
Corticosteroids can reduce the blood-glucose-lowering effect of insulin. Clinically important hyperglycaemia has been seen. Monitor CBG closely when corticosteroids are given to patients with diabetes.
Somatostatin analogues (octreotide and possibly lanreotide) may either increase or decrease the insulin requirements but most patients with type 1 diabetes are likely to require a reduction in insulin dose, with some studies suggesting a potential reduction of 50% in patients taking concomitant octreotide. Monitor CBG when somatostatin analogues are given to patients with diabetes.
Further information
Safe prescribing and administration of insulin
Insulin should be prescribed according to National Patient Safety Agency (NPSA) recommendations for safe use of insulin, with the brand name and units written in full.
Patients and nursing staff should be reminded of the importance of rotating injection sites within the same body region to reduce or prevent the risk of cutaneous amyloidosis and other skin reactions; injecting into an affected ‘lumpy’ area may reduce the effectiveness of insulin.
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 in patients with type 1 diabetes mellitus who have not received their long-acting insulin, in patients with type 1 diabetes mellitus who are expected to miss more than one meal, if emergency surgery or in people with poorly controlled diabetes mellitus (HbA1c >69mmol/mol)). Patients with type 2 diabetes mellitus who are expected to miss more than one meal should have VRIII if they develop hyperglycaemia (CBG >12mmol/L).
Continue insulin degludec at 80% of usual dose during treatment with VRIII to prevent hyperglycaemia and ketosis on cessation of VRIII. In patients with type 1 diabetes mellitus do not discontinue VRIII unless patient has received alternative subcutaneous insulin within the last 30 minutes.
Liver reduction diet (LRD)
Obese patients 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. The insulin degludec dose should be reduced by 50% when the LRD commences to compensate for the reduction in dietary intake.
Administration by district nursing team or nursing home
Ensure any instructions about temporary dose reductions are directly communicated to the relevant district nursing team or nursing home. In the case of district nurse administration an amended authorisation form is likely to be required to enable a different dose to be administered. If patients are due their dose in the morning but are due to be admitted to hospital early in the morning before the dose can be given, arrangements should be made for it to be given on admission.
References
Centre for Perioperative Care. Guideline for Perioperative Care for People with Diabetes Mellitus Undergoing Elective and Emergency Surgery (October 2023). Available at: https://cpoc.org.uk/guidelines-resources/guidelines [Accessed on 6th 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 6th February 2024]
Summary of Product Characteristics – Tresiba® (insulin degludec) 100 units/mL Pre filled (FlexTouch). Novo Nordisk Limited. Accessed via www.medicines.org.uk 06/02/2024 [date of revision of the text September 2022]
Insulin. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 6th February 2024]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 6th February 2024]
Summary of Product Characteristics – Xultophy® (liraglutide + insulin degludec) 100 units/ml + 3.6 mg/ml solution for injection. Novo Nordisk Limited. Accessed via www.medicines.org.uk 18/05/2024 [date of revision of the text February 2023]