Secretagogues and cardiac risk

Several studies have shown an increase in cardiac events associated with the use of secretagogues. These studies have included noninvasive cardiac studies and angioplasty studies. The exception was the United Kingdom Prospective Diabetes Study in which the subjects had recently diagnosed diabetes and were free of clinical manifestations of cardiovascular disease. The proposed mechanism for this increase is worsening myocardial ischemia as a result of the loss of ischemic preconditioning (brief periods of antecedent myocardial ischemia leading to amelioration of myocardial damage from prolonged ischemia) because of closure of adenosine triphosphate (ATP)-sensitive potassium channels in the myocardium. Diabetes itself can also adversely affect ischemic preconditioning. However, modern secretagogues such as glimepiride and nateglinide appear to exert desirable hypoglycemic effects by blocking pancreatic K-ATP channels without compromising ischemic preconditioning in the heart. We review the currently available literature on cardiac risk with secretagogues.