The addition of rosiglitazone (Avandia from GlaxoSmithKline) to glucose-lowering therapy in people with type 2 diabetes does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs, according to the RECORD trial in the June 20 edition of the Lancet.
Philip D. Home, MD, from the Newcastle Diabetes Centre and Newcastle University, in Newcastle upon Tyne, England, and colleagues sought to understand the cardiovascular outcomes with rosiglitazone in combination with metformin or sulfonylurea, compared with metformin and sulfonylurea dual therapy.
In a multicenter, open-label trial, the researchers randomly assigned 4,447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean glycated hemoglobin (HbA1C) of 7.9 percent to addition of rosiglitazone (2,220) or to a combination of metformin and sulfonylurea (active control group, 2,227).
The primary endpoint was cardiovascular hospitalization or cardiovascular death, with a hazard ratio (HR) noninferiority margin of 1.20.
The investigators found that a total of 321 people in the rosiglitazone group and 323 in the active control group experienced the primary outcome during a mean 5.5-year follow-up, meeting the criterion of noninferiority.
The hazard ratio was 0.84 for cardiovascular death, 1.14 for MI and 0.72 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, according to the authors.
Home and his colleagues also found that upper and distal lower limb fracture rates were increased mainly in women randomly assigned to rosiglitazone. Mean Hb1C was lower in the rosiglitazone group than in the control group at five years.
In an accompanying editorial, Debabrata Mukherjee, MD, a cardiologist with the University of Michigan Health System in Ann Arbor, wrote that the RECORD study was specifically designed to assess the effect of rosiglitazone on cardiovascular outcomes and demonstrated noninferiority for the primary endpoint of cardiovascular hospitalization or cardiovascular death. The addition of Avandia to glucose-lowering therapy in people with type 2 diabetes did increase the risk of heart failure and of some fractures, mainly in women.
Based on this study and other available evidence, Mukherjee said that Avandia is not recommended for people with a history of heart failure or with previous problems that might have led to myocardial dysfunction, and should also be used with caution in women at high risk of fractures.
Given the limitations of this open-label study and the fact that evidence is insufficient to rule out a small increased risk of MI caused by rosiglitazone when compared with other glucose-lowering agents, Mukherjee recommended that Avandia should be used with caution and with prudence in the management of type 2 diabetes.
The study was funded by the London-based GlaxoSmithKline.