Five types of oral
antihyperglycemic drugs are currently approved for the treatment of diabetes:
biguanides, sulfonylureas, meglitinides,
glitazones and
alpha-glucosidase inhibitors. We briefly review the cardiovascular effects of the most commonly used
antidiabetic drugs in these groups in an attempt to improve knowledge and awareness regarding their influences and potential risks when treating patients with
coronary artery disease (CAD). Regarding
biguanides, gastrointestinal disturbances such as
diarrhea are frequent, and the intestinal absorption of group
B vitamins and
folate is impaired during chronic
therapy. This deficiency may lead to increased plasma
homocysteine levels which, in turn, accelerate the progression of
vascular disease due to adverse effects on platelets,
clotting factors, and endothelium. The existence of a graded association between
homocysteine levels and overall mortality in patients with CAD is well established. In addition,
metformin may lead to lethal
lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as
heart failure or recent
myocardial infarction. Sulfonylureas avoid ischemic preconditioning. During
myocardial ischemia, they may prevent opening of the
ATP-dependent
potassium channels, impeding the necessary hyperpolarization that protects the cell by blocking
calcium influx. Meglitinides may exert similar effects due to their analogous mechanism of action. During treatment with
glitazones,
edema has been reported in 5% of patients, and these drugs are contraindicated in diabetics with NYHA class III or IV cardiac status. The long-term effects of
alpha-glucosidase inhibitors on morbidity and mortality rates and on diabetic micro- and macrovascular complications is still unknown. Combined sulfonylurea/
metformin therapy reveals additive effects on mortality. Four points should be mentioned: (1) the five oral
antidiabetic drug groups present proven or potential cardiac hazards; (2) these hazards are not mere 'side effects' but are deeply rooted in the drugs' mechanisms of action; (3) current data indicate that combined
glibenclamide/
metformin therapy seems to present a special risk and should be avoided in the long-term management of type 2 diabetics with proven CAD, and (4) Non-
Insulin Antidiabetic Therapy in Diabetic Cardiac Patients 155 customized
antihyperglycemic pharmacological approaches should be investigated for the optimal treatment of diabetic patients with
heart disease. New possibilities are represented by
incretin mimetic compounds,
dipeptidyl peptidase (DPP)-4 inhibitors, inhaled
insulin and eventually oral
insulin.