Exenatide (Byetta) and Liraglutide (Victoza) 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: 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 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: the person is intolerant of either metformin or a sulphonylurea, or treatment with metformin or a sulphonylurea is contraindicated, and the person is intolerant of thiazolidinediones and dipeptidyl peptidase-4 (DPP-4) inhibitors, or treatment with thiazolidinediones and DPP-4 inhibitors is contraindicated
Patient journey and monitoring Patients HbA1c not at target and treatment with OHA optimized Duration of diabetes <10 years Decision taken to commence GLP-1 within parameters defined above Carry out pre treatment HbA1c levels and weight and record. 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. Failure to comply with this means treatment will not be commenced. This is to ensure the best outcomes with the treatment are achieved. Patient is provided with patient information leaflet on GLP1 treatment. 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. 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 Recap with patient how to administer the s/c injection. Prescribe 2x 3mg penfill on acute This will allow dosing of ; 0.6mg for 7 days 1.2mg for 25 days Review and check for side effects and concordance in 1/52 via telephone and titrate Prescribe 2x3mg pen fill monthly (which will be sufficient for 1.2mg od dosing) on repeat to review in 5 months. Be careful not to choose the 3x3mg pen fill as this will result in wastage and an extra 39 month cost. Exenatide Recap with patient how to administer the s/c injection. Prescribe on acute x 1x pre-filled pen contains 60 doses of 5μg This will allow dosing of ; 30 days of 5μg bd 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. Prescribe 1x10μg pen fill monthly on repeat to review in 5 months.
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.
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.
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. http://www.nice.org.uk/guidance/index.jsp?action=download&o=44318 2. http://guidance.nice.org.uk/ta203/guidance/pdf/english 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.