Frequency of Inappropriate Metformin Prescriptions

Methods

We performed a retrospective chart review of patients receiving metformin through our outpatient pharmacy at an academic medical center. Institutional review board approval was obtained, and all patients with 2 or more prescriptions for metformin processed between January 1, 2000, and September 30, 2000, were identified. These patient records were randomized using a random number generator (SAS v6.12, SAS Institute Inc, Cary, NC).

The prevalence of inappropriate prescriptions for metformin was defined as the percent of patients receiving metformin who had documented CHF or renal dysfunction. Patients were considered to have CHF if the diagnosis was included in the medical problem list or clinic notes, and if they were taking medications for CHF (diuretics, angiotensin-converting enzyme inhibitors, digoxin). Renal dysfunction was defined as a serum creatinine greater than 1.5 mg/dL (132.6 µmol/L) for men and greater than 1.4 mg/dL (123.8 µmol/L) for women. Patient records were also reviewed for documentation of functional cardiac status or evidence that contraindications were considered.

Results

Pharmacy records identified 241 patients with 2 or more prescriptions for metformin; 100 of these were randomly selected for chart review. Twenty-two patients (22%; 95% confidence interval, 14%-30%) were found to have either CHF requiring medications or renal insufficiency. Of these 22 patients, 14 had CHF only, 5 had renal insufficiency only, and 3 had both. For patients with contraindications to metformin, the mean age was 60 years, 50% were women, and 50% were African American. These characteristics were similar for patients without contraindications. Patients with contraindications did have a significantly longer duration of diabetes (14.2 vs 6.4 years; P<.001).

Of the 17 patients with CHF, 4 patients had a documented New York Heart Association functional classification (class II: n = 2; class III: n = 2). Of the 8 patients with renal dysfunction, the mean serum creatinine was 1.8 mg/dL (159.1 µmol/L) and mean blood urea nitrogen was 27 mg/dL (9.639 mmol/L). Only 2 patients had documentation in the medical record that providers considered metformin contraindications.

Comment

In our review, almost one quarter of patients with a prescription for metformin had 1 or more absolute contraindications. Several recent studies in Europe have documented similar rates of inappropriate metformin prescribing.^{2, 5-6}

Adverse event reports suggest the incidence of metformin-associated lactic acidosis is between 1 in 10 000 to 1 in 100 000 patient-years.⁷ In the first 14 months after its release in the United States, the FDA received 47 confirmed cases of lactic acidosis associated with metformin, with a 42% mortality rate. More than 90% of patients had relative or absolute contraindications to metformin.³

Because our assessment of the prevalence of contraindications to metformin use relies on a chart review, it may underestimate the frequency of contraindications and it is difficult to determine whether clinicians are aware they are prescribing metformin against a black-box warning. Nonetheless, our results suggest that metformin frequently may be inappropriately prescribed despite black-box contraindications. Documentation of this potential risk in the medical record is limited and health care providers should consider improving the documentation of the risk of lactic acidosis and provide appropriate counseling for patients who receive the drug.