2000/026 NICE Issues Guidance on Rosiglitazone for Type 2 Diabetes

Ref: NICE 2000/026 Issued: 18 August 2000

The National Institute for Clinical Excellence has today issued its guidance on the use of the drug rosiglitazone for Type 2 diabetes. The guidance has been issued to all GPs, and Consultant grade diabetologists and endocrinologists in England and Wales

Type 2 diabetes occurs when the body cannot make enough insulin for its needs, or when the insulin that is produced does not work properly (known as insulin resistance). This type of diabetes usually appears in people over the age of 40 and it is thought to be a condition that affects about 800,000 people in England and Wales.

Rosiglitazone is one of a new class of glucose-lowering drugs; it can be taken orally and works by reducing the body's resistance to the action of insulin leading to a lowering of blood glucose.

In summary NICE has recommended that:

• Patients should be offered rosiglitazone combination therapy (as an alternative to injected insulin if:
• they are unable to take metformin and sulphonylurea (medicines that lower blood glucose levels) as a combination therapy, or
• their blood glucose remains high despite adequate trial of this combination treatment.
• The combination of rosiglitazone and metformin is preferred to the combination of rosiglitazone and a sulphonylurea - particularly for obese patients. Rosiglitazone plus sulphonylurea may be offered to patients who are unable to take metformin.

Andrew Dillon, the Institutes Chief Executive said, "This guidance is an example of the way NICE intends to support and promote clinically and cost effective new medicines at the time they become available. Our guidance should ensure uniform take up of rosiglitazone throughout the NHS."

Ends

Notes for Editors

1. Type 2 diabetes is a chronic metabolic disorder caused by defects in insulin secretion and action. The resulting build up of glucose in the blood (hyperglycaemia) can cause a range of diabetic complications, including damage to various organs, as small blood vessels or large arteries become narrow or blocked. Common diabetic complications are visual impairment, kidney failure, angina, myocardial infarction, stroke, foot ulceration and erectile dysfunction. People with Type 2 diabetes are at particularly high risk of cardiovascular disease. This appears to be related directly to hyperglycaemia, but also to hypertension and adverse lipid profiles.
2. Type 2 diabetes can be managed through diet and exercise alone, at least in the early stages. However, it is a progressive disease, and nearly all patients require oral glucose-lowering drugs (usually metformin or a sulphonylurea) after some time. Most patients eventually need insulin in order to maintain satisfactory blood glucose levels. Current treatment guidelines recommend a "step-up" policy, starting with advice on diet and exercise, adding oral glucose-lowering agents, first as monotherapy, then in combination, and finally insulin if blood glucose targets are not achieved.
3. Rosiglitazone is a thiazolidinedione, one of a new class of oral glucose-lowering drugs, the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, which work by reducing the body's resistance to the action of insulin.
4. Rosiglitazone is licensed for use in:
   "oral combination treatment of Type 2 diabetes mellitus in patients with insufficient glycaemic control despite maximal tolerated dose of oral monotherapy with either metformin or a sulphonylurea:
• in combination with metformin only in obese patients.
• in combination with a sulphonylurea only in patients who show intolerance to metformin or for whom metformin is contraindicated."
5. The manufacturer's Summary of Product Characteristics states that rosiglitazone is not recommended for use in combination with insulin. Rosiglitazone is contraindicated in patients with cardiac failure, hepatic impairment and severe renal insufficiency. Noted adverse events are fluid retention, anaemia, and weight gain.
6. The current UK price of rosiglitazone has been confirmed to the Department of Health as £0.95 for a 4 mg tablet. The incremental cost per patient of rosiglitazone add-on therapy will depend upon the average dose of rosiglitazone prescribed and upon the proportions of patients who would otherwise have received alternative add-on therapy or insulin. If 75% of patients on rosiglitazone were to take 4mg daily and 25% 8 mg daily (as suggested by the US experience), then the average annual cost of rosiglitazone would be £430 per patient. Estimates from the UKPDS study give the average annual cost of insulin therapy as £230 per patient (for 'intensive' control). Thus, if rosiglitazone were substituted for insulin therapy, as in the main recommendations, then this would cost an additional £200 per patient per annum. In addition, current recommendations for liver function testing for rosiglitazone treated patients would cost approximately £20 per patient in the first year. However, with more expensive insulin regimes it is possible that rosiglitazone could be cost neutral.
7. SmithKline Beecham estimates that 72,800 patients in England and Wales (68,250 in England and 4,550 in Wales) are potentially suitable for rosiglitazone treatment. This is based on the assumption that 35% of patients with Type 2 diabetes are on oral monotherapy, that 52% of these have inadequate control of blood glucose, and that 50% of these would fall within the license indication. This would cost an additional £13.6m for England and £0.9m for Wales if rosiglitazone is substituted for insulin, and if the mean cost of insulin therapy is £230.
8. The Royal College of General Practitioners is currently leading the development of guidelines on the management of Type 2 diabetes in collaboration with other Royal Colleges and Diabetes UK, as part of the NICE guidelines programme. The guideline on control of blood glucose levels is due to be published in late 2000.
9. The Guidance will be reviewed in August 2002.
10. This guidance means that no matter where they live in England or Wales, both patients and health professionals, have access to information on what the NHS considers to be best practice in the prescribing of rosiglitazone for individuals with type 2 diabetes.
11. Health professionals are expected to take the guidance fully into account when exercising their clinical judgement about the circumstances in which it is appropriate to prescribe rosiglitazone for individual patients. This guidance does not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.
12. The National Institute for Clinical Excellence (NICE) is a part of the NHS. Part of its work is technology appraisals. That is we use a team of experts to produce guidance for both the NHS and patients on medicines, medical equipment and clinical procedures based on evidence of clinical and cost effectiveness. Each appraisal takes around 12 months to complete and involves the manufacturers of the technology, patient groups and professional organisations.
13. NICE promotes clinical and cost effectiveness through its technology appraisals, clinical guidelines and audit tools. NICE supports the work of those who make the complex treatment decisions - doctors, nurses, and other health professionals. The needs of the patient are central to NICE's work, and the Institute has forged strong links with patient groups and representatives.
14. NICE appraises new and existing health technologies, as selected by the Department of Health and the National Assembly for Wales and advises the NHS on how these technologies can best be used. It is also responsible for the production of national clinical guidelines, promoting best practice throughout the NHS. To support and assess the implementation of such guidelines, NICE will produce audit tools for use in the clinical setting.
15. Copies of the full guidance and information for patients are available on the NICE web site (www.nice.org.uk).
16. The full Guidance and patient notes are also available from: