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The sulfonylurea controversy: more questions from the heart
1Department of Medicine, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905, USA.
Insights
Sulfonylurea drugs, used for type II diabetes, may increase heart attack risk by blocking a protective mechanism. This review explores how these common hypoglycemic agents could harm diabetic patients with heart disease.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus significantly increases cardiovascular morbidity and mortality.
- Sulfonylurea drugs are widely used oral hypoglycemic agents for type II diabetes.
- Previous observations suggested a link between sulfonylureas and increased cardiovascular mortality.
Purpose of the Study:
- To review the molecular and cellular pharmacodynamics of sulfonylurea drugs.
- To discuss the potential clinical consequences of sulfonylurea use in diabetic patients with heart disease.
- To explore the inhibition of adenosine triphosphate (ATP)-sensitive potassium channels by sulfonylureas.
Main Methods:
- Review of existing literature on sulfonylurea drug mechanisms.
- Analysis of the role of adenosine triphosphate (ATP)-sensitive potassium channels in pancreatic insulin release and cardiac protection.
- Examination of clinical data and hypotheses regarding cardiovascular outcomes in diabetic patients using sulfonylureas.
Main Results:
- Sulfonylureas inhibit adenosine triphosphate (ATP)-sensitive potassium channels.
- Inhibition of these channels in the pancreas stimulates insulin release.
- Inhibition of these channels in the heart prevents ischemic preconditioning, a protective mechanism against heart injury.
Conclusions:
- Sulfonylurea drugs may be harmful to diabetic patients with cardiac disease.
- The inhibition of cardiac adenosine triphosphate (ATP)-sensitive potassium channels by sulfonylureas may negate endogenous cardioprotective mechanisms.
- Further investigation is warranted to understand the clinical implications of sulfonylurea use in this patient population.
Abstract:
Myocardial ischemia and infarction are associated with substantially increased morbidity and mortality among patients with diabetes mellitus. Although many factors contribute to the increased morbidity and mortality, in patients with non-insulin-dependent (type II) diabetes mellitus, one contributor may be the use of sulfonylurea drugs, the most widely used oral hypoglycemic agents. Such a possibility, which first arose over a 25 years ago when it was observed that patients taking sulfonylurea drugs had increased cardiovascular mortality, has recently resurfaced after the discovery that sulfonylureas act by inhibiting adenosine triphosphate (ATP)-sensitive potassium channels. In the pancreas, inhibition of ATP-sensitive potassium channels induces release of insulin; but in the heart, inhibition of these channels prevents ischemic preconditioning, an endogenous cardioprotective mechanism that protects the heart from lethal injury. This review outlines the current understanding of the molecular and cellular pharmacodynamics of sulfonylurea drugs and discusses the potential clinical consequences of inhibition of ATP-sensitive potassium channels in the heart of diabetic patients with cardiac disease in whom the use of sulfonylureas may be harmful.