The Lancet, Early Online Publication, 5 June 2009
Home PD, Pocock SJ, Beck-Nielsen H, et al.
This study is registered with ClinicalTrials.gov, number NCT00379769.
Final results from the RECORD trial found no increase in the risk for cardiovascular (CV) hospitalization or death with rosiglitazone treatment, when added to standard metformin or sulfonylurea, in patients with Type 2 diabetes.
The results confirmed an increased risk for heart failure and, particularly in women, for some fractures associated with rosiglitazone use. The authors say the study “provides useful data to help clinicians and people with diabetes decide when it is not safe to use rosiglitazone.”
The RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes) trial included 4447 patients with Type 2 diabetes on a maximum tolerated dose of metformin or a sulfonylurea. Participants were randomly assigned to the addition of rosiglitazone to their original monotherapy (n=2220) or take the combination of metformin and sulfonylurea (active control, n=2227).
As previously reported by, an earlier, unplanned interim analysis of RECORD conducted in 2007 due to concerns raised about the safety of rosiglitazone found no evidence of an increase in CV risk.
Philip Home (The Medical School, Newcastle Upon Tyne, UK) and co-investigators reported the results of their final planned analysis, which they say includes 7935 (47%) person-years further follow-up, at the American Diabetes Association annual conference in New Orleans, Louisiana, USA. The results were simultaneously published online by The Lancet.
Over a mean of 5.5 years of follow-up, the primary outcome of CV death or hospitalization occurred in 321 patients in the rosiglitazone group versus 323 in the active control group, giving a hazard ratio (HR) of 0.99.
There were nonsignificant differences between rosiglitazone and active control groups for the individual endpoints CV death, (HR=0.84), myocardial infarction (HR=1.14), and stroke (HR=0.72), but rosiglitazone was associated with more than double the relative risk for heart failure (HR=2.10).
The overall incidence of bone fractures was higher in the rosiglitazone group than the active control group (risk ratio [RR]=1.57), with the relative risk higher in women than men (RR=1.82).
Underlining that rosiglitazone is already not recommended in people with heart failure or problems that might have caused myocardial dysfunction, the authors say that the drug should be used with caution in women at high risk for fractures. But they assert that, although a small increased risk for myocardial infarction caused by rosiglitazone when compared with other glucose-lowering agents cannot be ruled out, “rosiglitazone does not increase overall cardiovascular morbidity or mortality.”
In an accompanying Comment article, Ravi Retnakaran and Bernard Zinman, from Mount Sinai Hospital, Toronto and University of Toronto, Canada, suggested that half-maximum doses of rosiglitazone or pioglitazone in combination might be considered, on evidence that half-doses provide greater than half the glucose-lowering benefit, but with limited side effects.
“This combination therapy is currently being assessed for the prevention of diabetes in individuals with impaired glucose tolerance. If the efficacy of this strategy is confirmed, we might be able to find the optimal way to use this class of medications in the treatment of Type 2 diabetes,” they wrote.