Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD):
a multicentre, randomised, open-label trial
Home PD, Pocock SL, Beck-Nielsen H, et al. The Lancet, Early Online Publication, 5 June 2009 doi:10.1016/S0140-6736(09)60953-3

Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared with the combination of the two over 57 years of follow-up. We also assessed comparative safety.

In a multicentre, open-label trial, 4447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean haemoglobin A1c (HbA1c) of 79% were randomly assigned to addition of rosiglitazone (n=2220) or to a combination of metformin and sulfonylurea (active control group, n=2227). The primary endpoint was cardiovascular hospitalisation or cardiovascular death, with a hazard ratio (HR) non-inferiority margin of 120. Analysis was by intention to treat. This study is registered with, number NCT00379769.

321 people in the rosiglitazone group and 323 in the active control group experienced the primary outcome during a mean 55-year follow-up, meeting the criterion of non-inferiority (HR 099, 95% CI 085116). HR was 084 (059118) for cardiovascular death, 114 (080163) for myocardial infarction, and 072 (049106) for stroke. Heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the active control group (HR 210, 135327, risk difference per 1000 person-years 26, 1141). Upper and distal lower limb fracture rates were increased mainly in women randomly assigned to rosiglitazone. Mean HbA1c was lower in the rosiglitazone group than in the control group at 5 years.

Addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes is confirmed to increase the risk of heart failure and of some fractures, mainly in women. Although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs.