Abstract
Background
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.
Objective
The aim of this study was to evaluate US FDA-approved and off-label MET utilization in the US from 2000 to 2015.
Methods
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.
Results
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.
Conclusion
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.
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References
Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, et al. Metformin slows down aging and extends life span of female SHR mice. Cell Cycle. 2008;7(17):2769–73.
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403.
Luo Z, Zang M, Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol. 2010;6(3):457–70.
Ruiter R, Visser L, van Herk-Sukel MP, Coebergh JW, et al. Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives. Diabetes Care. 2012;35(1):119–24.
Libby G, Donnelly LA, Donnan PT, Alessi DR. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009;32(9):1620–5.
King P, Peacock I, Donnelly R. The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol. 1999;48(5):643–8.
Sharma M, Nazareth I, Petersen I, et al. Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study. BMJ Open. 2016;6:e010210.
National Diabetes Statistics Report. 2017: estimates of diabetes and its burden in the United States. Atlanta: Centers for Disease Control and Prevention; 2017.
Kashi Z, Mahrooz A, Kianmehr A, Alizadeh A. The role of MET response in lipid metabolism in patients with recent-onset type 2 diabetes: HbA1c level as a criterion for designating patients as responders or nonresponders to MET. PLoS One. 2016;11(3):e0151543.
Anurag P, Anuradha CV. MET improves lipid metabolism and attenuates lipid peroxidation in high fructose-fed rats. Diabetes Obes Metab. 2012;4(1):36–42.
Nesti L, Natali A. MET effects on the heart and the cardiovascular system: a review of experimental and clinical data. Nutri Metab Cardiovasc Dis. 2017;27(8):657–69.
Evans JM, Donnelly LA, Emslie-Smith AM, et al. MET and reduced risk of cancer in diabetic patients. BMJ. 2005;330:1304–5.
Wang T, McNeill AM, Chen Y, Senderak M, Shankar RR, et al. MET prescription patterns among US adolescents aged 10-19 years: 2009–2013. J Clin Pharm Ther. 2016;41(2):229–36.
Hsia Y, Dawoud D, Sutcliffe AG, Viner R, et al. Unlicensed use of MET in children and adolescents in the UK. J Clin Pharmacol. 2012;73(1):1365–2125.
Tahereh N, Bayat R, Hamedi M. MET therapy in girls with polycystic ovary syndrome: a self-controlled trial. Arch Iranian Med. 2007;10(2):176–81.
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No sources of funding were used for this study.
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Samantha Le and Grace C. Lee have no conflicts of interest to declare.
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This study is Institutional Review Board exempt.
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Since this study analyzed anonymised data, no formal consent was required.
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Le, S., Lee, G.C. Emerging Trends in Metformin Prescribing in the United States from 2000 to 2015. Clin Drug Investig 39, 757–763 (2019). https://doi.org/10.1007/s40261-019-00799-0
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DOI: https://doi.org/10.1007/s40261-019-00799-0