Emerging Trends in Metformin Prescribing in the United States from 2000 to 2015

Metformin (MET) is used as first-line treatment for type 2 diabetes mellitus but has been shown to have pleiotropic effects that have expanded its use to various conditions. Limited current data exist regarding unconventional use within various patient populations.

The aim of this study was to evaluate US FDA-approved and off-label MET utilization in the US from 2000 to 2015.

We performed a retrospective analysis of outpatient MET prescribing in the US from 2000 to 2015. Data from the Medical Expenditure Panel Survey (MEPS) administered by the Agency of Healthcare Research and Quality were analyzed. Demographic characteristics, including age, sex, socioeconomic status, comorbidities, and region, were analyzed using the MEPS Household Component (HC). Prescription rates were defined as the annual number of MET prescriptions divided by the corresponding population estimate. Population denominators were derived using the MEPS HC. The MEPS estimates US populations based on sampled persons in the target population (civilian, non-institutionalized) for an entire year. MET prescribing is represented by population per 1000 persons. We determined if changes of MET prescribing were uniform across five age groups: < 18 years, 18-29 years, 30-49 years, 50-64 years, and 64 years and older.

An estimated 553,291,094 MET prescriptions were dispensed in the US from 2000 to 2015. Prescribing rates steadily increased from 2000 to 2015. FDA-approved MET prescription rates increased from 2.27 per 1000 persons in 2000 to 235 per 1000 persons in 2015, while off-label MET prescription rates increased from 0.74 per 1000 persons in 2000 to 20.3 per 1000 persons in 2015. The top indications for off-label MET use were endocrine disorders (45.8%), cardiovascular disorders (18.2%), female reproductive disorders (12.9%), and metabolic disorders (10.9%). MET prescribing rates for FDA-approved indications increased across all age groups in 2000 and 2015, with the most substantial increase seen in adults aged 50-64 years and > 65 years (1.7 per 1000 persons to 20.6 per 1000 persons, and 2.3 per 1000 persons to 18.7 per 1000 persons, respectively). While off-label MET increased across all age groups from 2000 to 2015, a tenfold increase (< 1.0 to 10.6) was seen in adults aged 30-49 years of age.

Overall, MET use has substantially increased within the past 15 years, which was mainly driven by older adults. Our study highlights the emerging prevalence of MET use in both FDA-approved and off-label indications.