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Glitazones No Better than Older Drugs for Type 2 Diabetes

Posted: Friday, April 18, 2008

The class of glitazone diabetes drugs offer no benefits as monotherapy compared with older, less expensive drugs, according to the authors of an analysis of data from recent clinical trials.

Available evidence supports the use of rosiglitazone and pioglitazone in combination with metformin or an oral sulfonylurea only in type 2 patients who are intolerant of or otherwise unable to take one of the other drugs, the authors conclude.

"There is no convincing evidence that [glitazones] offer any benefits over metformin or a sulphonylurea in terms of improved clinical outcomes when used as monotherapy," the authors concluded. "Evidence for their use in triple therapy is also weak, and they should be reserved for patients in whom insulin is contraindicated or is likely to be poorly tolerated."

The conclusions mirror those from a 2001 report from the same group. In that earlier report, the authors also concluded that use of rosiglitazone and pioglitazone should be limited to two-drug combinations in patients who could not take metformin or a sulfonylurea.

In the current review the authors analyzed findings from studies published since the earlier review. They examined the effects of the glitazones on various clinical outcomes in patients with type 2 diabetes.

The analysis showed:

The two available glitazones reduced hemoglobin A1c to a similar degree and significantly better than placebo.
Glitazones demonstrated no advantages over other oral agents with respect to hypoglycemic activity.
Fixed-dose combination drugs containing a glitazone demonstrated no advantages over the individual drugs.
A suggestion of an increased risk of cardiovascular events with glitazones
An association with fluid retention and congestive heart failure
An increased fracture risk A hint of an association with macular edema

"If a glitazone is thought to be necessary, pioglitazone is probably safer, but should only be used as an adjunct to other hypoglycemic drugs where there is a contraindication or intolerance to metformin or sulphonylureas," the authors concluded.

According to the authors, the European Medicines Agency Committee for Medicinal Products in Humans concluded in 2007 that the risks of the glitazones outweigh their benefits.

The Medicines and Healthcare products Regulatory Agency also has issued an advisory stating that rosiglitazone might be associated with a small increased risk of cardiac ischemia and should be used in patients with ischemic heart disease only after "careful evaluation of individual risk."

Source: Diabetes In Control: Drug and Therapeutics Bulletin - "Glitazones in type 2 diabetes: an update" Drug Ther Bull 2008; 46: 25-29.