Oct. 27, 2008 -- A review of 40 clinical drug trials failed to produce reliable conclusions about the effects of oral diabetes medicines on cardiovascular health, despite controversy over the drug Avandia.
The analysis of the trials, 27 ofthem lasting under a year, is reported in today's edition of Archives of Internal Medicine.
Researchers, led by Elizabeth Selvin, PhD, MPH, set out to evaluate how a group of newer and more expensive drugs that came to market beginning in 1995 compared with older medications used to treat type 2 diabetes. Avandia is one of the newer medications. An earlier study also looked at whether Avandia was riskier than other diabetes drugs.
Despite a finding that the drug trials, most of them short-term, were not comprehensive enough to yield the best data, researchers point to metformin as a drug that is "moderately protective" and Avandia as "possibly harmful."
The earlier analysis of the effect of diabetes drugs on cardiovascular health, reported in TheNew England Journal of Medicine in 2007, showed that Avandia, which works well to reduce blood sugar, was associated with a higher risk of heart attack. However, researchers in that case also acknowledged that their conclusions were limited by a lack of access to original clinical data.
In the Johns Hopkins study, researchers did not find a significant difference between the ill or beneficial cardiovascular effects of any of the diabetes drugs. The relatively small differences in blood pressure, cholesterol levels, and weight observed after treatment with various diabetes medications in the clinical trials "may not translate to changes in long-term cardiovascular health," the study says.
The trials that Selvin and her colleagues reviewed were done to assess the benefit or harm of oral diabetes medications approved in the U.S., including combinations of drug therapy. Participants ranged from 52 to 69, and 27 of the 40 trials followed patients for a year or less.
In a critical editorial accompanying the analysis, David M. Nathan, MD, of the Diabetes Center at Massachusetts General Hospital in Boston, calls the current approach to assessing the adverse effects of diabetes drugs "unsatisfactory."
"In the end, owing in part to the limited information of the generally short-term studies included in this and other meta-analyses, the conclusions drawn will be disappointing for health practitioners who want a clear answer to the question, 'Is it safe?'" Nathan writes.
He advises increasing the size and duration of clinical trials with a uniform, standardized collection of adverse outcome data to identify "relatively rare complications before the drugs are used by millions."