Glipizide and metformin and Cardiovascular risk

The use of oral hypoglycemic agents may be associated with an increased risk of cardiovascular mortality compared to treatment with diet alone or diet with insulin. This warning is based on the University Group Diabetes Program (UGDP) study, a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. Patients treated with diet plus a fixed dosage of either tolbutamide (a sulfonylurea) or phenformin (a biguanide) for 5 to 8 years had a cardiovascular mortality rate approximately 2.5 times that of patients treated with diet alone, resulting in discontinuation of both these treatments in the study. Despite controversy regarding interpretation of these results, clinicians and patients should be aware of the potential risk when making treatment decisions for diabetes, particularly in the presence of underlying cardiovascular disease. Data are not available for other sulfonylureas or biguanides, nor for hypoglycemic agents belonging to other classes. However, given the similarities in chemical structure and/or mode of action, the same caution should be applied.