The study recruited 4,447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy. The study was open label and last for a mean of 5.5 years. The primary outcome was cardiovascular death or hospital admission.
Participants in the study were randomly assigned to treatment with dual therapy of metformin and sulphonylurea or initial monotherapy (metformin or sulphonylurea) and rosiglitazone.
The primary outcome occurred in 321 patients taking a rosiglitazone combination and 323 patients in the active control. The difference was not significant and therefore rosiglitazone treatment was found to be non-inferior.
The study did find an increased risk of heart failure requiring hospital admission (Hazard Ratio 2.10, 95% confidence interval [CI] 1.35—3.27, p=0.001) and of fracture (risk ratio 1.57, 95% CI 1.26–1.97, p<0.0001).
It is also interesting to note that a greater proportion of participants treated with rosiglitazone were also treated with cardiovascular drugs by the end of the study. In particular, 9.2% more patients were using a statin (55.2% versus 46.0%) and 4.9% more were using loop diuretics (13.0% versus 8.1%).
The authors conclude that, "rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs" with a caveat that, "the data are inconclusive about any possible effect on myocardial infarction.
The results of this study are consistent with what is currently known. Glitazones increase the risk of heart failure and fractures. Rosiglitazone has also been suspected of increasing the risk of heart attacks and while this study indicates no increased risk of cardiovascular death an increase in heart attacks cannot be discounted.
Action: Clinicians should continue to implement the existing guidelines. Glitazones (and gliptins) are considered as alternatives to metformin or sulphonylureas when these agents are contraindicated or poorly tolerated. Pioglitazone currently has fewer prescribing restrictions and may be a better choice where a glitazone is indicated.