Rosiglitazone (Avandia) Seen No Better than Other Drugs in Diabetic Control

DUSSELDORF, Germany, July 18 -- Diabetes patients treated with rosiglitazone (Avandia) did no better than those treated with other drugs, according to a Cochrane systematic review of 18 published trials.

The data from 8,432 patients found that glycemic control, as measured by levels of HbA1c, was no better in patients given rosiglitazone than those given other antidiabetic drugs, found Bernd Richter, M.D., of the University of Duesseldorf, and colleagues.

But the authors did not weigh in on the issue of potentially increased cardiovascular risk because they said the studies reviewed reported on 26 weeks or less of rosiglitazone therapy, which was not enough time to evaluate mortality, diabetes-related morbidity, or quality of life.

They concluded that "new studies should focus on patient-oriented outcomes to clarify the benefit-risk radio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public."

But in a statement, Dr. Richter raised doubts about the likelihood of such studies noting that "it is questionable whether new studies with rosiglitazone will be ethical given the fact that less dangerous therapeutic alternatives exist."

In many ways the Cochrane review echoed conclusions of a systematic review published Monday in the Annals of Internal Medicine which found that older drugs were as effective as rosiglitazone and pioglitazone and were less expensive as well. ( See For Type 2 Diabetes, Older Drugs Seem Tried and True)

Both reviews are likely to be added to the data that an FDA advisory panel will tackle on July 30 when it meets to consider concerns about the cardiovascular safety of rosiglitazone.

The cardiovascular safety furor was ignited by publication of a meta-analysis of 42 trials that found a 43% increase in relative risk of myocardial infarction for type 2 diabetes patients treated with rosiglitazone.

The odds ratio for MI was 1.43 (95% confidence interval 1.03-1.98, P=0.03), said Steven E. Nissen, M.D., of the Cleveland Clinic, lead author of the meta-analysis, which was released online in May and in the June 14 print issue of the New England Journal of Medicine. (See Meta-Analysis Links Rosiglitazone (Avandia) to Risk of Myocardial Infarction)

According to information obtained by the Associated Press through a Freedom of Information request, the FDA received reports of 90 heart attacks among rosiglitazone users during the 35 days after publication of the Nissen study, versus only five rosiglitazone-linked heart attacks during the 35 days prior to the study's release. Likewise, heart-related hospitalizations increased from 11 to 126.

Nonetheless, sorting through the rosiglitazone data is no easy task, as illustrated by the way in which Dr. Richter and colleagues viewed data from the ADOPT trial in their Cochrane analysis. Interpretation can rest in the eye of the beholder.

Dr. Richter cited ADOPT (A Diabetes Outcomes Progression Trial) as the "single large randomized controlled trial that indicated increased cardiovascular risk" among the 18 trials included in his review. ADOPT also linked rosiglitazone to increased fracture risk in women, they reported.

But in a letter to The Lancet, Ronald L. Krall, M.D., chief medical officer of GlaxoSmithKline, maker of rosiglitazone, used the same ADOPT trial to make a case for the safety of rosiglitazone.

Dr. Krall said a post hoc analysis of ADOPT data "adjusted for medication exposure, found that such events [myocardial infarctions] were rare in this population and that all treatments were comparable."

ADOPT compared rosiglitazone to metformin or glyburide. The hazard ratios "varied from 0.58 to 1.52 and 95% CIs for all comparisons included unity," Dr. Krall wrote. (See Drug-Maker Defends Rosiglitazone in Letter to The Lancet)