Exenatide (byetta) and liraglutide (victoza)  prescribing guidance: notes for initiation in primary care

Exenatide (Byetta)T and Liraglutide (Victoza) T prescribing guidance:
Notes for initiation in primary care

These incretin mimetics are given by subcutaneous injection once or twice daily. They have
similar licenses; dual therapy with metformin or a sulphonylurea , for patients with insufficient
glycaemic control despite maximally tolerated doses, or for triple therapy with metformin and
a sulphonylurea, or metformin and a glitazone, for patients with insufficient glycaemic control
despite dual therapy.
Until November 2010 initiation was carried out by the Salford Community Health Diabetes
Team. However, the decision has been taken to move the initiation of GLP1s to GPs. These
guidance notes will help with identifying when they can be used and what to prescribe and
monitor to show effectiveness of therapy. If patients are not achieving the targets, as
defined by NICE, Liraglutide or Exanitide treatment should be stopped
.
When can they be used?
NICE reviewed the place of therapy of Exenatide in its guidance Type 2 diabetes- newer
agents [1] issued in June 2009 and also Liraglutide in a Technology Appraisal [2] issued in
October 2010 and concluded that it would be funded for use in the NHS for the following;
Exenatide Triple therapy
Exenatide to first-line metformin and a second-line sulfonylurea when control of blood glucose
remains or becomes inadequate (HbA1c = 7.5%, or other higher level agreed with the
individual) and the person has:
• a body mass index (BMI) = 35.0 kg/m2 in those of European descent (with appropriate
adjustment for other ethnic groups) and specific psychological or medical problems
associated with high body weight, or
• a BMI < 35.0 kg/m2 and therapy with insulin would have significant occupational implications
or weight loss would benefit other significant obesity-related comorbidities
Liraglutide Triple Therapy
Liraglutide 1.2 mg daily in triple therapy regimens (in combination with metformin and a
sulfonylurea, or metformin and a thiazolidinedione) is recommended as an option for the
treatment of people with type 2 diabetes, only when control of blood glucose remains or
becomes inadequate (HbA1c = 7.5% [<59mmol/mol], or other higher level agreed with the
individual), and the person has:
y a body mass index (BMI) = 35 kg/m2 in those of European descent (with appropriate
adjustment for other ethnic groups) and specific psychological or medical problems
associated with high body weight, or
y a BMI < 35 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities
Liraglutide Dual Therapy
Liraglutide 1.2 mg daily in dual therapy regimens (in combination with metformin or a
sulphonylurea) is recommended as an option, only if:
y the person is intolerant of either metformin or a sulphonylurea, or treatment with
metformin or a sulphonylurea is contraindicated, and
y the person is intolerant of thiazolidinediones and dipeptidyl peptidase-4 (DPP-4)
inhibitors, or treatment with thiazolidinediones and DPP-4 inhibitors is contraindicated
Issued by Medicines Management Team and Diabetes Interface Group November 2010 Review date November 2012
Patient journey and monitoring

y Patients HbA1c not at target and treatment with OHA optimized
y Duration of diabetes <10 years
y Decision taken to commence GLP-1 within parameters defined above
y Carry out pre treatment HbA1c levels and weight and record. y Refer to SCH Diabetes team for X-pert diabetes education programme (stating for GLP-1 start.) Injection technique and disposal of sharps will be covered in the programme. y Failure to comply with this means treatment will not be commenced. This is to ensure the best outcomes with the treatment are achieved. y Patient is provided with patient information leaflet on GLP1 treatment.
y Explain to the patient that if treatment goals of reduction in weight and reduction in
HbA1c level are not reached on treatment it will be stopped as it is not working.
y SCH Diabetes team will confirm attendance at X-Pert programme in writing, documenting required HbA1c target (>1% reduction) and weight target (>3% reduction). Copy of targets will be given to patient. GP practice will commence Liraglutide or Exenatide
Liraglutide

Ö Recap with patient how to administer the s/c injection.
Ö Prescribe 2x 3mg penfill on acute
Ö Review and check for side effects and concordance in 1/52 via telephone and titrate Ö Prescribe 2x3mg pen fill monthly (which will be sufficient for 1.2mg od dosing) on repeat
Be careful not to choose the 3x3mg pen fill as this will result in wastage and an extra
£39 month cost.

Exenatide

Ö Recap with patient how to administer the s/c injection.
Ö Prescribe on acute x 1x pre-filled pen contains 60 doses of 5μg This will allow dosing of ; 30 days of 5μg bd Ö Review and check for side effects and concordance in 1/12 via telephone. Increase dose to 10μg bd and inform patient that they will be issued with a 10μg pen on next prescription. 1x10μg pen fill monthly on repeat to review in 5 months. Issued by Medicines Management Team and Diabetes Interface Group November 2010 Review date November 2012 Patient is reviewed in practice at 6 months and HbA1c and weight are checked
Continue with GLP-1 Treatment only if patient has achieved agreed targets of 3% weight loss
and >1% HbA1c reduction.
IN BOTH THE ABOVE NOT ACHIEVED STOP GLP-1 AND REFER TO DIABETES TEAM

If agreed targets achieved but glycaemic control > 58mmol/mol (7.5%) contact Salford
Community Health Diabetes Team for treatment advice
If patients continue on GLP1 review again in 6 months time and review against parameters as defined above to ensure control is being maintained. Issued by Medicines Management Team and Diabetes Interface Group November 2010 Review date November 2012 Further Information on Liraglutide

Presentation
Prefilled, disposable pen device comprising a pen injector and cartridge.
Each pen contains 3 ml solution (6mg/ml) , delivering 30 doses of 0.6 mg, 15 doses of 1.2 mg
or 10 doses of 1.8 mg. It is available in two pack sizes: 2 x 3 ml prefilled pens (£78.48), and 3
x 3 ml prefilled pens (£117.72)
Dosing schedule
Liraglutide is administered once daily at any time, independent of meals by subcutaneous
injection in the abdomen, in the thigh or in the upper arm. The injection site and timing can be
changed without dose adjustment. However, it is preferable that Liraglutide is injected around
the same time of the day. The recommended starting dosage is liraglutide 0.6 mg daily. After
at least 1 week, the dose should be increased to 1.2 mg.
It is licensed at 1.8mg od however, the 1.8mg dose has not been deemed a cost effective use
of NHS resources by NICE as results from meta analysis have shown no differences between
1.2mg and 1.8mg in terms of reductions in HbA1c levels. If patient is not achieving
treatment goals on 1.2mg dose do not increase to 1.8mg; follow the algorithm above.
Cost
The drug costs for liraglutide are
1.2 mg dose £954.84 per year
1.8 mg dose £1432.26 per year
Safety data
There is currently no long term safety data for Liraglutide and it has no studies showing
outcomes on diabetes related mortality and morbidity, only data showing its effect on HbA1c
and weight. It is a black triangle drug and so all adverse effects (even if predicted) should be
reported via the yellow card system.
Common side effects
The main side effect is nausea.
Others include; diarrhoea, vomiting, constipation, abdominal pain, and dyspepsia. These
gastrointestinal adverse effects may occur more frequently at the start of treatment with
liraglutide, and usually diminish within a few days or weeks on continued treatment.
Hypoglycaemia may also be common, and is more common when liraglutide is used in
combination with a sulphonylurea.
Patient should be advised to ‘stick with’ treatment during the first few weeks as unpleasant
effects are likely to diminish with time.
Benefits to weight loss
These are not uniform and tend to be greater in those with a higher BMI at the start of
treatment. They should not be used to promote weight loss in patients whose HbA1c is at
target, even on the advice of secondary care.
Issued by Medicines Management Team and Diabetes Interface Group November 2010 Review date November 2012 Further Information on Exenatide
Presentation
Each cartridge is assembled into a disposable pen-injector (pen).
Each pre-filled pen contains 60 doses of sterile preserved solution (approximately 1.2ml [5μg]
or 2.4ml [10μg]. Injection needles are not included. The following are examples of disposable
needles that can be used with the BYETTA pen: 29, 30, or 31 gauge (diameter 0.25-0.33mm)
and 12.7, 8, or 5mm length.
Dosing schedule
5μg bd can be increased to 10μg to further improve glycaemic control.

Cost
The drug costs for Exenatide are
5μg bd dose £818.88 per year
10 μg bd dose £818.88 per year

Safety data
There is currently no long term safety data for Exanatide and it has no studies showing
outcomes on diabetes related mortality and morbidity, only data showing its effect on HbA1c
and weight. It is a black triangle drug and so all adverse effects (even if predicted) should be
reported via the yellow card system.
Common side effects
The main side effect is nausea.
Others include; diarrhoea, vomiting, constipation, abdominal pain, and dyspepsia. These
gastrointestinal adverse effects may occur more frequently at the start of treatment with
Exenatide, and usually diminish within a few days or weeks on continued treatment.
Hypoglycaemia may also be common, and is more common when Exenatide is used in
combination with a sulphonylurea.
Patient should be advised to ‘stick with’ treatment during the first few weeks as unpleasant
effects are likely to diminish with time.

References
1. 2.
If you have any queries regarding the use of GLP1s please contact the Salford Community
Health Diabetes team on 0161 212 2095 or the Medicines Management team on 0161 212
4245.
Issued by Medicines Management Team and Diabetes Interface Group November 2010 Review date November 2012

Source: http://www.salforddiabetescare.co.uk/admin/resources/uploaded/GLP-1%20initiation%20pathway%20and%20guidance%20from%20Medicines%20Management453.pdf

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