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Brands of this drug

Abasaglar®, Lantus®, Semglee®, Toujeo®

Combination product: Suliqua®

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 or during liver reduction diet (LRD) in patients undergoing bariatric surgery.

For Suliqua® – dehydration (including renal impairment / acute renal failure) if continued (see Further information).

For Suliqua® – potential risk of aspiration and post-operative nausea and vomiting (PONV) if continued (see Further information).

For Suliqua® – delay in absorption of some medicines due to delay in gastric emptying if continued (see Further information).

Advice in the perioperative period

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:

• Suliqua® (insulin glargine with lixisenatide) – follow advice in table below but see Further information and Perioperative considerations for consideration about lixisenatide component.

When reducing insulin doses round to the nearest whole unit. The dose of Suliqua® 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).

NB: The advice is also the same regardless of whether insulin glargine 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 (in the 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 glargine 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 glargine 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 Suliqua®)

An individualised risk assessment should take place for patients taking Suliqua® (contains lixisenatide) 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

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 glargine post-operatively. Blood glucose should be monitored until eating habits and food intake stabilises. If there is a need to recommence insulin glargine 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.

Gastric emptying (for Suliqua®)

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.

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.

European Medicines Agency Guidance on prevention of medication errors with high-strength insulins

A high-strength insulin is a medicine that contains insulin at a concentration of more than the standard 100 units/ml. There are differences in the way high-strength insulin products are used compared with existing insulin formulations of standard-strength and there is therefore a risk of medication errors and accidental mix-up.

Advice for healthcare professionals:

• A syringe must NEVER be used to withdraw insulin from a pre-filled pen otherwise severe overdose can result
• Insulin must always be prescribed in units (spelled out in full) and include the dose frequency
• The strength of the insulin formulation should always be included in the prescription

Lantus® (insulin glargine 100 units/ml) and Toujeo® (insulin glargine 300 units/ml) are NOT bioequivalent and are NOT directly interchangeable.

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 glargine 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 glargine dose should be reduced by 50% when the LRD commences to compensate for the reduction in dietary intake.

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

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 two doses are missed, there may be a need for gradual reintroduction post-operatively to avoid common side-effects associated with initiation or 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.

Dehydration (for Suliqua®)

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. 

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 – ABASAGLAR® (insulin glargine) 100 units/mL solution for injection in a cartridge. Eli Lilly and Company Limited. Accessed via www.medicines.org.uk 06/02/2024 [date of revision of the text January 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 – Suliqua® (insulin glargine + lixisentaide) 100 units/ml + 33 micrograms/ml solution for injection in a pre-filled pen. SANOFI. Accessed via www.medicines.org.uk 06/02/2024 [date of revision of the text July 2023]

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