Using rosiglitazone (Avandia) in combination with standard diabetes treatments (metformin or a sulfonylurea) to lower blood glucose in type 2 diabetics does not increase the risk of cardiovascular (CV) disease or death. However, the RECORD study confirmed that using Avandia more than doubles the risk of heart failure, and increases the risk of fractures, mainly in women, according to an online published account June 5 in Lancet, and simultaneously presented at the American Diabetes Association (ADA) meeting in New Orleans.
Rosiglitazone belongs to a class of drugs called thiazolidinediones, and has been proven by numerous studies as an effective agent to control blood glucose. However, some studies have suggested an increased risk of heart attacks caused by the rosiglitazone, and concern about adverse effects has reduced its use, according to the authors.
In the randomized trial, Philip Home, PhD, from the Medical School at Newcastle University in Newcastle Upon Tyne, England, and colleagues examined 4,447 patients with type 2 diabetes already on either metformin or a sulfonylurea with a mean hemoglobin A1c concentration (HbA1c) of 7.9 percent. They assigned patients an addition of either Avandia (2,220 patients) or to a combination of metformin and sulfonylurea in the control group (2,227). The primary endpoint was cardiovascular hospitalization or cardiovascular death.
The researchers found that 321 people in the Avandia reached the primary endpoint compared with 323 in the control group, indicating no statistically significant difference.
However, they also found that heart failure causing admission to hospital or death occurred in 61 people in the Avandia group and 29 in the control group--thus risk of heart failure was more than doubled for Avandia patients. The risk of arm and lower leg fractures also increased by 57 percent in patients given rosiglitazone--although the increased risk for women (82 percent) was much higher than that for men (23 percent).
"It is good to have robust evidence that this useful medication does perform similarly to other glucose-lowering medications in regard to cardiovascular events," the authors wrote. "It is also good to see it perform better in controlling blood glucose in the longer term. The data on fractures and heart failure are known class effects, and here the study provides useful data to help clinicians and people with diabetes decide when it is not safe to use rosiglitazone."
They concluded that Avandia is "not recommended for people with a history of heart failure or with previous problems that might have led to myocardial dysfunction. Rosiglitazone should be used with caution in women at high risk of fractures. Although our evidence is insufficient to rule out a small increased risk of MI caused by rosiglitazone when compared with other glucose-lowering agents, rosiglitazone does not increase overall cardiovascular morbidity or mortality."
In an accompanying commentary, Ravi Retnakaran, MD, and Bernard Zinman, MD, from Mount Sinai Hospital in Toronto, wrote that half-maximum doses of rosiglitazone (or a related drug, pioglitazone) in combination therapy could be considered as it is generally accepted that half-doses give better-than-half results, while limiting side-effects. They concluded: "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."