In 1995, biguanide metformin was approved by the U.S. Food and Drug Administration for use in the treatment of type 2 diabetes. Use of biguanide phenformin in the 1970s led to its subsequent withdrawal from the market in many countries because of a high incidence of lactic acidosis in patients with renal impairment, hepatic dysfunction or cardiac disease. Sulkin and associates studied the prevalence of conditions currently regarded as contraindications or cautions to the use of metformin in patients receiving this agent.
The authors identified the following potential contraindications or cautions to metformin therapy: (1) renal impairment, defined as a plasma creatinine level greater than 1.4 mg per dL (120 μmol per L) or dipstick-positive proteinuria, (2) cardiac failure, (3) chronic hepatic dysfunction, (4) significant chronic pulmonary disease, (5) coronary artery disease, (6) peripheral vascular disease, and (7) miscellaneous conditions (intercurrent illnesses, acute trauma or major surgical procedures, and metastatic malignancy).
The authors reviewed the medical records of 89 patients receiving metformin to identify the prevalence of potential contraindications to the use of the drug. These patients were seen at a university hospital diabetes clinic in the United Kingdom. The authors found that over one half of the patients had conditions regarded as cautions or contraindications to the use of metformin, eight of the patients had two conditions, five patients had three conditions and one patient had four conditions. The most common conditions were peripheral vascular disease (22 patients), ischemic heart disease (20 patients) and proteinuria (14 patients). Two of the patients had a significant degree of renal impairment.
The authors conclude that metformin should be used with caution in such high-risk patients until data from large clinical trials provide further information on the risks and benefits of metformin therapy.
EDITOR'S NOTE: While the clinical characteristics of type 2 diabetes may vary between the patients in this study and those seen by family physicians in the United States, it is important for clinicians to recognize potential contraindications to the use of metformin and prevent drug-related morbidity. We should remain vigilant and exercise caution before prescribing metformin.—j.n.