A CLASS of novel, oral anti-diabetic agents that treat the symptoms of type 2 diabetes has been introduced by Smithkline Beecham. The drug, called Avandia (rosiglitazone maleate), is a new thiazolidinedione.
Avandia also targets insulin resistance -- the failure of the body to respond adequately to its own insulin. By contrast, most older therapies for type 2 diabetes exert their effects primarily through different mechanisms. Metformin, for example, acts by reducing glucose output from the liver; sulfonylureas by stimulating the pancreas to produce more insulin and insulin injections by taking the place of the natural insulin that the pancreas can no longer produce.
Avandia improves blood sugar control in combination with other diabetes medications, according to studies presented at the annual scientific sessions of the American Diabetes Association (ADA). These studies showed that Avandia in combination with sulfonylureas or insulin, provides better control than can be achieved with these treatments alone.
The maximum dose of Avandia used in sulfonylurea combination studies was 4 mg/day. These studies evaluated the efficacy of this combination and the potential for hypoglycaemia. In the patients that received sulfonylurea alone there was little change in haemoglobin. A1c, a measure of glucose levels over time or fasting plasma glucose. The addition of 4 mg/day of Avandia to therapy in those patients inadequately controlled on sulfonylurea produced significant improvements in both haemoglobin A1c and fasting plasma glucose. Proportions of patients with symptoms of hypoglycaemia were similar in all treatment groups.
Avandia can also be used in combination with metformin. In a study of 348 patients inadequately controlled on the maximum daily dose of metformin, the addition of 8 mg/day of Avandia produced a drop in haemoglobin A1c of 1.2 percentage points versus metformin alone. The estimate of beta-cell function in the 8 mg/day Avandia plus metformin group increased by 94.2 per cent and insulin resistance decreased by 20.4 per cent versus no change in the metformin only group.
No evidence of drug-related liver damage was seen in more than 4,500 patients treated with Avandia as monotherapy, in combination with sulfonylureas and in combination with metformin. Patients had regular blood tests designed to detect liver damage. According to data presented at the meeting, patients being treated for more than six months and many for more than one year have shown no signs of liver damage. In the new studies, Avandia in combination with insulin, no patient has shown signs of drug-related liver toxicity.
