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Long-acting Insulin

 

Abasaglar® [insulin glargine], Humulin® I [isophane insulin], Insulatard® [isophane insulin], Insuman® Basal [isophane insulin], Lantus® [insulin glargine], Levemir® [insulin detemir], Semglee® [insulin glargine], Suliqua® [insulin glargine with lixisenatide], Tresiba® [insulin degludec], Toujeo® [insulin glargine], Xultophy® [insulin degludec with liraglutide]

[This monograph covers LONG-ACTING insulin – the advice is the same regardless of whether it is part of a basal-bolus regimen in type 1 diabetes or monotherapy / add-on therapy for type 2 diabetes]

 

  Issues for Surgery


Hypoglycaemia if continued during nil by mouth period / during liver reduction diet (LRD) for patients undergoing Bariatric Surgery.

Increased risk of post-operative infection and delayed wound healing due to poor glycaemic control if discontinued.

Increased risk of Diabetic Ketoacidosis (DKA) if discontinued, particularly in patients with type 1 diabetes.

  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.

Elective Surgery 

Continue, but at a reduced dose (including combination products containing Glucagon-Like Peptide 1 (GLP-1) receptor agonists) - see figure 1 below for details of dose reduction.

When reducing insulin doses round to the nearest unit. 

EXCEPT: -

  • Patients undergoing Bariatric Surgery – see below

Figure 1 – Management of LONG-ACTING insulin in the Perioperative Period1

Combination Products: -

The doses of Suliqua® and Xultophy® are expressed in terms of ‘dose steps’ (where 10 dose steps refers to 10 units of insulin). 

Consideration should be given to prescribing the components of combination products as separate medicines perioperatively.

Patients undergoing Bariatric Surgery
Patients with type 1 diabetes mellitus need an individualised management plan formulated with the Diabetes Specialist Team.

Patients with type 2 diabetes mellitus commencing on liver reduction diet (LRD): Give 50% of usual dose when LRD commences, with close monitoring of CBG2 (see Further Information). When reducing insulin doses round to the nearest unit.  For patients who are taking combination products, the long-acting insulin should be prescribed separately perioperatively so that adjustment to the insulin dose can be made. See also Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists monograph .

Patients with type 2 diabetes mellitus not following a LRD: Follow the advice in figure 1 above for Elective Surgery.

Emergency Surgery
Monitor CBG, ketones, renal profile and lactate on admission to exclude DKA or hyperosmolar hyperglycaemic state (HHS)1. 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 Information1. Continue to monitor ketones if CBG >13mmol/mol1.

Perioperative Considerations
Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated, with the patient’s LONG-ACTING insulin continued at 80% of their usual pre-operative dose1 (see figure 1 above and Further Information).

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

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 diabetic regimen1. 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 necessary1, 3.

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 should be reviewed by the Diabetes Specialist Team post-operatively.

Patients with type 2 diabetes should initially withhold their long-acting insulin post-operatively. Blood glucose should be monitored until eating habits and food intake stabilises2. If there is a need to recommence long-acting insulin post-operatively the dose should be tapered on discharge with strict blood glucose monitoring to avoid hypoglycaemia.  Patients should have their need for ongoing pharmacological management of their diabetes reviewed by their General Practitioner / Bariatric Surgical Team. 

  Interaction(s) with Common Anaesthetic Agents 


Reduction in Blood-Glucose Lowering Effect
Substances that may reduce the blood-glucose-lowering effect of insulin include sympathomimetics (e.g. epinephrine / adrenaline)4, 5, 6, 7, 8, 9, 10.

  Interaction(s) 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)4, 5, 7, 8, 9, 10, 11.

Reduction of Blood-Glucose Lowering Effect
Corticosteroids can reduce the blood-glucose-lowering effect of insulin4, 5, 6, 7, 8, 9, 10, 12. Clinically important hyperglycaemia has been seen12. Monitor CBG closely when corticosteroids are given to patients with diabetes13.

Somatostatin analogues (octreotide and possibly lanreotide) may either increase or decrease the insulin requirements5, 7, 9, 10, 11 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 octreotide12, 13.  Monitor CBG when somatostatin analogues are given to patients with diabetes13.

  Further Information


Safe Prescribing and Administration of Insulin
European Medicines Agency – Guidance on prevention of medication errors with high-strength insulins14

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 interchangeable4, 6.

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 insulin3.

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 who have not received their long-acting insulin, in patients with type 1 diabetes who are expected to miss more than one meal, 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 (CBG >12mmol/L)1.

Continue long-acting insulin at 80% of usual dose during treatment with VRIII to prevent hyperglycaemia and ketosis on cessation of VRIII1.  In patients with type 1 diabetes do not discontinue VRIII unless patient has received alternative subcutaneous insulin within the last 30 minutes1.

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. The long-acting insulin dose should be reduced by 50% when the LRD commences to compensate for the reduction in dietary intake2.

  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 – Lantus® (insulin glargine) 100 Units/ml solution for injection in Solostar pre-filled pen. SANOFI. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text August 2020]
  5. Summary of Product Characteristics – Levemir® (insulin detemir) InnoLet 100 units/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]
  6. Summary of Product Characteristics – Toujeo® (insulin glargine) 300units/ml SoloStar, 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]
  7. Summary of Product Characteristics – HUMULIN® I (isophane) 100IU/ml suspension for injection in cartridge. Eli Lilly and Company Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text August 2020]
  8. Summary of Product Characteristics – Insuman® Basal (isophane) SoloStar 100 IU/ml suspension 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]
  9. 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 28/02/2021 [date of revision of the text September 2020]
  10. Summary of Product Characteristics – Tresiba® (insulin degludec) 100 units/ml Pre filled (FlexTouch). Novo Nordisk Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text November 2020]
  11. Summary of Product Characteristics – Insulatard® (isophane) Penfill 100 international units/ml suspension for injection in cartridge. Novo Nordisk Limited. Accessed via www.medicines.org.uk 28/02/2021 [date of revision of the text September 2020]
  12. Insulin. 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. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 28th February 2021]
  14. European Medicines Agency: Guidance on prevention of medication errors with high-strength insulins. 27 November 2015. Available at: www.ema.europa.eu [Accessed 28th February 2021)
Lantus® [insulin glargine] Toujeo [insulin glargine] Levemir® [insulin detemir] Tresiba® [insulin degludec] Insulatard® [human insulin] Humulin® I [human insulin] Insuman® Basal [human insulin] Suliqua® [insulin glargine with lixisenatide] Xultophy® [insulin degludec with liraglutide] Abasaglar® [insulin glargine] Semglee® [insulin glargine]