Cardiovascular Safety of Oral Antidiabetic Agents: The Insulin Secretagogues

The prevalence of type 2 diabetes mellitus (T2DM) has increased rapidly over the past decade. In the Untied States, this increase has been greater than 40%. Obesity, which is closely linked to risk of developing T2DM, has likewise increased in prevalence by more than 60% during the same time period. Cardiovascular disease is the major cause of mortality among patients with T2DM, accounting for 60–80% of deaths in these patients.1 Blood glucose control has been shown to decrease the risk of microvascular complications of diabetes.2 Whether blood glucose control decreases the risk of cardiovascular mortality in these patients has been more difficult to establish, but data such as those from the landmark United Kingdom Prospective Diabetes Study (UKPDS) suggest that good glycemic control probably does decrease cardiovascular risk in patients with T2DM.3 In the UKPDS, a regimen of more aggressive glycemic control was associated with a 16% reduction in risk for myocardial infarction (MI), including fatal and nonfatal MI and sudden death. While this reduction just missed statistical significance (P = 0.052), a more recent analysis of the UKPDS results showed that, for each 1% reduction in glycated hemoglobin, there was a 14% reduction in MI risk.4 Despite recent studies demonstrating the likely benefit of good glycemic control in decreasing cardiovascular risk in T2DM, there have been lingering concerns about potential adverse cardiovascular effects of insulin secretagogues, specifically sulfonylureas. Concern