NICE Appraisal of liraglutide for Type 2 Diabetes Mellitus
LONDON, June 14, 2010--In preliminary draft guidance published today (14 June 2010), NICE recommends liraglutide 1.2 mg daily for some people with type 2 diabetes mellitus. However, it does not recommend liraglutide at 1.8mg daily, as the available evidence does not suggest any significant additional benefit with the higher dose.
Liraglutide is recommended in dual therapy regimens for people who would normally receive both metformin and a sulphonylurea, but who cannot tolerate one or other of these drugs. For these people, liraglutide can be given in combination with either metformin or a sulphonylurea.
As part of triple therapy regimens, liraglutide 1.2mg daily is recommended (in combination with metformin and sulfonylurea or metformin and a thiazolidinedione) only when control of blood glucose remains or becomes inadequate(HbA1c ≥ 7.5%, or other higher level agreed with the individual). The patient being treated must also have a body mass index (BMI) of ≥ 35kg/m2 (in those of European descent, and appropriate adjustments made for other ethnic groups), and specific psychological or medical problems associated with high body weight. Liraglutide is also recommended for patients with a BMI ≤ 35 kg/m2, where insulin therapy would have significant occupational implications, or weight loss would benefit other significant obesity-related comorbidities.
Treatment with liraglutide 1.2 mg daily in dual and triple therapy regimens should only be continued if the person’s diabetes has shown a beneficial metabolic response (defined as a reduction of at least 1% in HbA1c) and, in the case of triple therapy regimens, if the patient has weight loss of at least 3% of initial body weight at 6 months.
However, NICE is minded not to recommend liraglutide 1.8mg as a treatment option for people with type 2 diabetes. The independent Appraisal Committee felt that because the clinical data showed that there was only a marginal benefit from using the higher dose of liraglutide 1.8mg compared with liraglutide 1.2mg, treatment with the higher dose was not justified.
Dr Carole Longson, Health Technology Evaluation Centre Director at NICE said: “The incidence of type 2 diabetes is on the increase in England and Wales - and sadly so too are the complications of the disease. We are pleased, therefore, to recommend liraglutide 1.2 mg daily as a clinically and cost effective treatment option as part of both dual and triple therapy regimens for some patients with type 2 diabetes mellitus under restrictions. However we felt unable to recommend use of the higher dose as the available evidence does not suggest any significant additional benefit.”
This draft guidance has been issued for consultation; NICE has not yet issued final guidance to the NHS.
The first consultation on the provisional guidance for liraglutide for type 2 diabetes closed on 5 March. The Committee recommended that NICE requested further clarification from the manufacturer of liraglutide (Novo Nordisk), with respect to the use of liraglutide in dual therapy regimens. Novo Nordisk submitted a response to this request but also supplied further analyses over and above that requested. In accordance with the guide to the single technology appraisal process (section 3.5.34), NICE had to extend the timelines for this appraisal to allow for a full and comprehensive review of this new evidence. The second discussion of this topic took place on 20 April 2010. Final guidance is likely to be published in October 2010
Notes to Editors
About the appraisal
- The appraisal consultation document (ACD) is available for comment from 14 June to 5 July at http://guidance.nice.org.uk/TA/Wave20/68
- After consultation the Appraisal Committee will meet again to consider the evidence, this appraisal consultation document and any comments from the consultees.
- Type 2 diabetes: newer agents (partial update of CG66), NICE clinical guideline 87 (2009) available at http://guidance.nice.org.uk/CG87
- Liraglutide is administered once daily as a subcutaneous (under the skin) injection. The recommended starting dosage is liraglutide 0.6 mg daily. After at least 1 week, the dose should be increased to 1.2 mg. Based on clinical response, after at least 1 week the dose can be increased to 1.8 mg. Daily doses higher than 1.8 mg are not recommended.
- Liraglutide is available in a prefilled, disposable pen device comprising a pen injector and cartridge. The pen holds 3 ml of solution and contains 18 mg of liraglutide. Each pen holds 30 doses of 0.6 mg, 15 doses of 1.2 mg, or 10 doses of 1.8 mg. Dose is specified by the user and can be adjusted before use. It is available in two pack sizes: 2 x 3 ml prefilled pens (£78.48), and 3 x 3 ml pens (£117.72) (British National Formulary [BNF 59] March, 2010). The drug costs for liraglutide as reported by the manufacturer are £2.62 and £3.92 per day (1.2 mg dose and 1.8 mg dose, respectively), and £954.84 and £1432.26 per year (1.2 mg dose and 1.8 mg dose, respectively). Costs may vary in different settings because of negotiated procurement discounts.
- The most frequently reported adverse effects of liraglutide are gastrointestinal, including nausea, diarrhoea, vomiting, constipation, abdominal pain, and dyspepsia (indigestion). 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 (low blood sugar) is also common, especially so when liraglutide is used in combination with a sulphonylurea.
- The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.
- NICE produces guidance in three areas of health:
- public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector.
- health technologies - guidance on the use of new and existing medicines, treatments and procedures within the NHS.
- clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.
 Liraglutide works by stimulating the release of insulin; it also reduces the appetite and therefore food intake by slowing gastric emptying.
 Metformin, sulphonylurea and thiazolidinedione are a class of drugs that are used in the management of type 2 diabetes mellitus and lower glucose levels in the blood.
 The Committee noted that the results of a meta-analysis presented in the Evidence Review Group (ERG) showed no significant difference between liraglutide 1.2mg and liraglutide 1.8mg in terms of patients reaching an HbA1c level of less than 7%.
Posted: June 2010
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