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Dipeptidylpeptidase-4 (DPP-IV) Inhibitors (Gliptins)

 

Alogliptin, Linagliptin, Saxagliptin, Sitagliptin, Vildagliptin


  Issues for Surgery


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

Potential for hypoglycaemia when taken concomitantly with other blood glucose lowering medicines and continued during nil by mouth period.

Combination products containing Metformin – risk of lactic acidosis if continued (see Interaction(s) with other Common Medicines used in the Perioperative Period and Further Information).

Combination products containing Dapagliflozin or Empagliflozin – risk of diabetic ketoacidosis (DKA), volume depletion, hypotension and / or electrolyte disturbances if continued (see Further Information).

  Advice in the Perioperative period


Elective and Emergency Surgery
DDP-IV Inhibitors should be taken as normal the day prior to surgery1.

EXCEPT:

Morning or Afternoon Surgery
Continue1, 2.

EXCEPT:

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

Patients undergoing Bariatric Surgery
Patients with type 2 diabetes mellitus commencing liver reduction diet (LRD): Consideration should be given to stopping DDP-IV Inhibitors when the LRD commences, with close monitoring of capillary blood glucose (CBG)3 (see Further Information).

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

Perioperative Considerations
Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated (see Further Information) and withhold DPP-IV Inhibitor during VRIII treatment1.

Ensure emergency treatment of hypoglycaemia is prescribed i.e. Glucogel® and 20% dextrose. Rapid acting insulin should also be prescribed1, 2.

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

For combination products containing metformin – follow advice in Metformin monograph.

For combination products containing SGLT-2 Inhibitors – follow advice in Sodium Glucose Co-transporter 2 (SGLT-2) Inhibitors monograph.

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 DDP-IV Inhibitors 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 / Bariatric Surgical Team.

  Interaction(s) with Common Anaesthetic Agents


None for products containing DDP-IV Inhibitor alone2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

Hypotension
Combination products containing a SGLT-2 inhibitor can increase the risk of hypotension when used concomitantly with inhalational or intravenous anaesthetics2.

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


None for products containing DPP-IV Inhibitor alone2, 4, 6, 8, 11, 13.

Iodinated Contrast Agents
Caution with combination products containing metformin and concomitant use of iodinated contrast agents5, 7, 9, 12, 14 – see Metformin monograph .

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)
Caution with combination products containing metformin and concomitant use of NSAIDs5, 7, 9, 12, 14 – see Metformin monograph .

Hypotension
Combination products containing a SGLT-2 inhibitor can increase the risk of hypotension when used concomitantly with the antiemetics droperidol and prochlorperazine2.

  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 (capillary blood glucose (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. Whilst DDP-IV inhibitors do not cause hypoglycaemia, the reduction in dietary intake means they are unlikely to have any benefit.

Lactic Acidosis
Risk of lactic acidosis with combination products containing metformin5, 7, 9, 12, 14 – see Metformin monograph .

DKA, Volume Depletion, Hypotension and / or Electrolyte Imbalance
Risk of DKA, volume depletion, hypotension and / or electrolyte imbalance with combination product containing dapagliflozin or empagliflozin10, 15 – see Sodium Glucose Co-transporter 2 (SGLT-2) Inhibitors monograph.   

  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. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 27th February 2021]
  3. 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
  4. Summary of Product Characteristics – Vipidia® (alogliptin) 12.5mg film-coated tablets. Takeda UK Ltd. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text June 2018]
  5. Summary of Product Characteristics – Vipdomet® (alogliptin + metformin) 12.5mg/1000mg film coated tablets. Takeda UK Ltd. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text July 2018]
  6. Summary of Product Characteristics – Trajenta® (linagliptin) 5mg film-coated tablets. Boehringer Ingelheim Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text October 2019]
  7. Summary of Product Characteristics – Jentadueto® (linagliptin + metformin) 2.5mg/1,000mg Film-coated Tablets. Boehringer Ingelheim Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text April 2020]
  8. Summary of Product Characteristics – Onglyza® (saxagliptin) 2.5mg film-coated tablets. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text March 2020]
  9. Summary of Product Characteristics – Komboglyze® (saxagliptin + metformin) 2.5mg/1,000mg film-coated tablets. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text March 2020]
  10. Summary of Product Characteristics – Qtern® (saxagliptin + dapagliflozin) 5mg/10mg film-coated tablets. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text March 2020]
  11. Summary of Product Characteristics – Januvia® (sitagliptin) 100mg film-coated tablets. Merck Sharp & Dohme (UK) Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text May 2020]
  12. Summary of Product Characteristics – Janumet® (sitagliptin + metformin) 50mg/1000mg film-coated tablets. Merck Sharp & Dohme (UK) Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text September 2020]
  13. Summary of Product Characteristics – Galvus ® (vildagliptin) 50mg Tablets. Novartis Pharmaceuticals UK Ltd. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text October 2020]
  14. Summary of Product Characteristics – Eucreas® (vildagliptin + metformin) 50mg/1000mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text May 2020] 
  15. Summary of Product Characteristics – Glyxambi® (linagliptin + empagliflozin) 10mg/5mg Film-coated Tablets. Boehringer-Ingelheim Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text October 2020]



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