Meglitinides

Nateglinide, Repaglinide

  Issues for Surgery

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

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

  Advice in the Perioperative period

Elective Surgery
Meglitinides should be taken as normal the day prior to surgery¹ – EXCEPT for patients undergoing Bariatric Surgery, see below.

Morning Surgery
Omit morning dose if nil by mouth^{1, 2}.

Afternoon Surgery
Take morning dose if eating^{1, 2}.

Patients undergoing Bariatric Surgery
Patients with type 2 diabetes mellitus commencing liver reduction diet (LRD): Consideration should be given to stopping meglitinides when the LRD commences, with close monitoring of capillary blood glucose (CBG)² (see Further Information).

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

Emergency Surgery

In the event of emergency surgery and the patient has already taken their meglitinide dose monitor capillary blood glucose (CBG) levels closely and treat any hypoglycaemia accordingly.

Perioperative Considerations
Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated (see Further Information) and omit meglitinide during VRIII treatment¹.

Ensure emergency treatment of hypoglycaemia is prescribed i.e. Glucogel^® and 20% dextrose. Rapid acting insulin should also be prescribed^{1, 2}.

Post-operative Advice
Restart once eating and drinking normally and VRIII (where applicable) has been stopped¹.

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 meglitinides should be considered post-operatively³. Blood glucose should be monitored until eating habits and food intake stabilises³. Patients should have their need for ongoing pharmacological management of their diabetes reviewed by their General Practitioner and / or Bariatric Surgical Team. 

  Interaction(s) with Common Anaesthetic Agents

 
None^{3, 4, 5, 6, 7}.

  Interaction(s) with other Common Medicines used in the Perioperative Period

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)
Caution with concomitant use of NSAIDs – may enhance the hypoglycaemic effect of meglitinides^{4, 5}.

Antibiotics
Clarithromycin and trimethoprim slightly increase the exposure to repaglinide^{2, 4, 6, 7}. As infections can increase blood glucose concentrations this is not thought to be clinically significant; however, there are case reports of hypoglycaemia with concurrent use⁷. If concurrent use of clarithromycin, erythromycin, trimethoprim or co-trimoxazole is deemed necessary – monitor CBG closely and adjust repaglinide dose if necessary⁶.

  Further Information

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))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. 

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.

  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 8^th March 2021]
2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 27^th February 2021]
3. Busetto L, Dicker D, Aznar 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
4. Summary of Product Characteristics - Starlix^® (nateglinide). Novartis Pharmaceuticals UK Ltd. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text June 2015]
5. Summary of Product Characteristics - Prandin^® (repaglinide) 1mg tablets. Novo Nordisk Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text May 2016]
6. Repaglinide. 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 1^st March 2021]
7. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 27^th February 2021]