Glucagon-like Peptide-1 (GLP-1) Analogues

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GLP-1 analogues: 

 FIRST-LINE:   Liraglutide
 SECOND-LINE:    Exenatide
 THIRD-LINE:  Dulaglutide

            

                         

Prescribing Information

S LIRAGLUTIDE injection 18mg/3mL pre-filled pen

Dose:  by subcutaneous injection, 600 micrograms once daily, at the same time each day, independent of meals.  The dose may be increased if necessary at an interval of at least 1 week to 1·2mg. In exceptional circumstances a maximum dose of 1·8mg once daily may be used.

S EXENATIDE injection, pre-filled pen 5 micrograms/dose, 10 micrograms/dose; modified-release injection 2mg/pre-filled pen

Dose:  by subcutaneous injection 

Normal release: initially 5 micrograms twice daily within 1 hour before 2 main meals (at least 6 hours apart), increased if necessary after at least 1 month to maximum 10 micrograms twice daily.   Some oral medications should be taken at least 1 hour before or 4 hours after exenatide injection; consult product literature for details. 

Modified-release: for use in patients with compliance problems, needle phobia or where weekly administration by the district nurse etc would be advantageous. By subcutaneous injection, 2mg once weekly on the same day each week. To be administered at any time of day, with or without meals. The day of weekly administration can be changed if necessary as long as the next dose is administered at least 24 hours after the next dose is due. Effect may continue for up to 10 weeks after discontinuation. 

S DULAGLUTIDE injection, pre-filled pen 0·75mg/dose, 1·5mg/dose

Dose:  by subcutaneous injection

As monotherapy when metformin is inappropriate, 750 micrograms once weekly.

As add on therapy, 1·5mg once weekly, however consider a starting dose of 750 micrograms once weekly for potentially vulnerable populations such as those aged 75 years or over. If adding to existing metformin and/or pioglitazone therapy, continue the current dose of metformin/pioglitazone. If adding to existing therapy of a sulfonylurea or insulin, consider a lower dose of sulfonylurea/insulin to reduce the risk of hypoglycaemia.

 

Indications
  • For use in individuals with type 2 diabetes of less than 10 years duration and BMI 30kg/m2 or over
  • Third-line agent in addition to (metformin + sulfonylurea) OR (metformin + pioglitazone) OR (metformin + dapagliflozin)* OR (metformin + insulin)# OR (pioglitazone + insulin)# where HbA1c is above target of 58mmol/mol
  • Fourth-line agent in addition to (metformin + pioglitazone + insulin) # OR (metformin + dapagliflozin + insulin)*.

*Licence for dapagliflozin. #Licence for exenatide.

Contra-Indications
  • Insulin deficiency or ketoacidosis
  • Pregnancy, breast-feeding and children under 18 years
  • Severe gastro-intestinal disease including gastroparesis and inflammatory bowel disease
  • Previous history of pancreatitis.
Renal Impairment

LIRAGLUTIDE

  • Avoid if eGFR less than 30mL/min

EXENATIDE

  • Use in caution in patients aged 70 years or over if eGFR 30 to 50mL/min
  • Avoid if eGFR less than 30mL/min (standard preparation). Avoid if eGFR <50mL/min (weekly preparation).

DULAGLUTIDE

  • Avoid if eGFR less than 30mL/min.
Clinical review
  • Review effect of therapy after 6 months
  • Expected beneficial effects:
 HbA1c:    

Reduction of 11mmol/mol (1%)

OR treatment target of <59mmol/mol met 

 Weight:  

 Reduction of 3% of initial weight

    

              

Considerations for clinical review

Review effect of therapy after 6 months using traffice-light table below:

 

Further review
  • Consider other factors which may preclude the use of insulin – for example occupation, social situation and ability to cope with insulin.
Further information
  • It is expected that contra-indications and interactions as per the BNF will be assessed for patients on an individual basis prior to prescribing any medication.
  • Please refer to the Highland Formulary, www.sign.ac.uk, www.nice.org.uk and www.rcplondon.ac.uk for further information.