Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Actos (Eli Lilly Australia)
15 mg, 30 mg and 45 mg tablets
Approved indication: type 2 diabetes
Australian Medicines Handbook Section 10.1

Many patients with type 2 diabetes cannot control their glucose concentrations with diet alone. These patients have insulin resistance which may benefit from treatment with a thiazolidinedione.

The thiazolidinediones act on the peroxisome proliferator-activated receptor.1 This leads to an increased sensitivity of muscle and adipose tissue to insulin. The drugs also reduce gluconeogenesis in the liver.

Although there are few published studies, pioglitazone has been approved for use as monotherapy or in combination with other drugs, including insulin, for the treatment of type 2 diabetes. This approval appears to be based on clinical trials lasting 16 or 26 weeks.

The studies using pioglitazone as monotherapy found that it had a significantly greater effect, than a placebo, on fasting blood glucose and HbA1C.In combination with a sulfonylurea, or metformin, pioglitazone will produce greater reductions in fasting blood glucose and HbA1C than a placebo. Similar effects were seen when pioglitazone was given to patients who were already taking insulin for their type 2 diabetes.

Patients taking insulin should start with a lower dose (15 mg) of pioglitazone. The recommended dose when pioglitazone is used in combination with other drugs is 30 mg.

Pioglitazone can be given once a day. Although it has a half-life of 5-6 hours, pioglitazone has an active metabolite which has a half-life of 16-23 hours.

Following the serious adverse reactions which lead to the withdrawal of troglitazone, there is concern about the hepatotoxicity of the thiazolidinediones. Similar adverse effects were not reported during the trials of pioglitazone, but liver function must be monitored regularly. During the first year of treatment the liver function should be tested every eight weeks.

The thiazolidinediones also alter lipid metabolism. This may include an increase in low density lipoprotein. In animal studies there has been cardiac hypertrophy. Although echo cardiographic studies have not shown this effect in humans, the studies have excluded patients with heart disease.

More common adverse effects include oedema, headache and myalgia. Less than4% of the patients in the clinical trials withdrew because of adverse effects.

Although cytochrome P450 3A4 is involved in the metabolism of pioglitazone there are no studies of interactions with other drugs metabolised by this enzyme. Pioglitazone may reduce the effectiveness of oral contraception. While it does not alter the steady-state pharmacokinetics of metformin and glipizide caution is needed when combining drugs such as these with pioglitazone. The combination with an oral hypoglycaemic drug or insulin increases the risk of hypoglycaemia.

To ascertain the role of pioglitazone there is a need for comparative studies to be published. There is currently not enough evidence to suggest that pioglitazone should become the first-line treatment after diet fails to control a patient's blood glucose.