Study confirms sulfonylurea risks

A retrospective analysis of more than 90,000 people with diabetes has confirmed that sulfonylureas are associated with an excess all-cause mortality risk, and - in line with international recommendations – recommends metformin as a first line treatment for type 2 diabetes. Compared with metformin, monotherapy with first and second generation sulfonylureas resulted in a 24% to 61% excess risk for all cause mortality and second-generation sulfonylureas were associated with an 18% to 30% excess risk for CHF, the researchers found. Compared with metformin survival was significantly better with pioglitazone. A higher risk was seen with rosiglitazone compared with pioglitazone, however, this risk was not significant in a fully adjusted statistical model. At odds with recent studies, the British researchers found no statistically significant increase in the risk of MI from treatment with glitazones in general or from rosiglitazone. The researchers noted that their findings agree with American Diabetes Association recommendations that favour metformin as the initial treatment for type 2 diabetes but “do not confirm previous reports of an excess risk of myocardial infarction associated with rosiglitazone compared to metformin”. While the authors said they had accounted for a large number of potential confounders the possibility of residual confounding or confounding by indication could not be excluded. Professor of endocrinology at Garven Institute of Medical Research and St Vincent’s Hospital, Dr Don Chisholm, told Cardiology Update the study should be interpreted with “caution” because it does not show cardiac failure events that are likely to occur with the use of glitazones. “This study fails to show these considerations which suggests there are some difficulties with ascertainment,” he said. “And while there are alternatives to use in place of metformin that each have their own side effects, it is harder to make interpretations about the effectiveness of other drugs.” “However, sulfonylureas may have less optimal cardiovascular outcomes and put patients at risk of hypoglycaemia… so at the end of the day, this study is correct in reinforcing the almost universal advice to use metformin as a first line drug.” BMJ 2009; published online before print...