The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Metformin and the Risk of Cancer
Open accessAbstract
OBJECTIVE: Time-related biases in observational studies of drug effects have been described extensively in different therapeutic areas but less so in diabetes. Immortal time bias, time-window bias, and time-lag bias all tend to greatly exaggerate the benefits observed with a drug. RESEARCH DESIGN AND METHODS: These time-related biases are described and shown to be prominent in observational studies that have associated metformin with impressive reductions in the incidence of and mortality from cancer. As a consequence, metformin received much attention as a potential anticancer agent; these observational studies sparked the conduction of randomized, controlled trials of metformin as cancer treatment. However, the spectacular effects reported in these studies are compatible with time-related biases. RESULTS: We found that 13 observational studies suffered from immortal time bias; 9 studies had not considered time-window bias, whereas other studies did not consider inherent time-lagging issues when comparing the first-line treatment metformin with second- or third-line treatments. These studies, subject to time-related biases that are avoidable with proper study design and data analysis, led to illusory extraordinarily significant effects, with reductions in cancer risk with metformin ranging from 20 to 94%. Three studies that avoided these biases reported no effect of metformin use on cancer incidence. CONCLUSIONS: Although observational studies are important to better understand the effects of drugs, their proper design and analysis is essential to avoid major time-related biases. With respect to metformin, the scientific evidence of its potential beneficial effects on cancer would need to be reassessed critically before embarking on further long and expensive trials.
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Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., & Zinman, B. (2009) · Diabetes Care · doi:10.2337/dc08-9025 · Cited by 3,834
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388
Immortal Time Bias in Pharmacoepidemiology
Suissa, S. (2008) · American Journal of Epidemiology · doi:10.1093/aje/kwm324 · Cited by 1,708
Self-citationThe influence of glucose-lowering therapies on cancer risk in type 2 diabetes
Currie, C. J., Poole, C. D., & Gale, E. A. M. (2009) · Diabetologia · doi:10.1007/s00125-009-1440-6 · Cited by 1,124
New Users of Metformin Are at Low Risk of Incident Cancer
Libby, G., Donnelly, L. A., Donnan, P. T., Alessi, D. R., Morris, A. D., & Evans, J. M. M. (2009) · Diabetes Care · doi:10.2337/dc08-2175 · Cited by 996
Bowker, S. L., Majumdar, S. R., Veugelers, P., & Johnson, J. A. (2006) · Diabetes Care · doi:10.2337/diacare.29.02.06.dc05-1558 · Cited by 933
Buzzai, M., Jones, R. G., Amaravadi, R. K., Lum, J. J., DeBerardinis, R. J., Zhao, F., Viollet, B., & Thompson, C. B. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4447 · Cited by 923
Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis
DeCensi, A., Puntoni, M., Goodwin, P., Cazzaniga, M., Gennari, A., Bonanni, B., & Gandini, S. (2010) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0157 · Cited by 918
Sahra, I. B., Laurent, K., Loubat, A., Giorgetti-Peraldi, S., Colosetti, P., Auberger, P., Tanti, J. F., Le Marchand-Brustel, Y., & Bost, F. (2008) · Oncogene · doi:10.1038/sj.onc.1211024 · Cited by 861
Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., & Zinman, B. (2009) · Diabetologia · doi:10.1007/s00125-008-1157-y · Cited by 712
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The burden and risks of emerging complications of diabetes mellitus
Tomic, D., Shaw, J. E., & Magliano, D. J. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00690-7 · Cited by 1,163
Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria
Bridges, H. R., Jones, A. J. Y., Pollak, M. N., & Hirst, J. (2014) · Biochemical Journal · doi:10.1042/bj20140620 · Cited by 661
Metformin in Cancer Treatment and Prevention
Morales, D. R., & Morris, A. D. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-062613-093128 · Cited by 484
Gandini, S., Puntoni, M., Heckman-Stoddard, B. M., Dunn, B. K., Ford, L., DeCensi, A., & Szabo, E. (2014) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-13-0424 · Cited by 457
Metadata
- Authors
- Suissa, S., & Azoulay, L.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2012-11-14
- Volume
- 35
- Issue
- 12
- Pages
- 2665-2673
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2013047715
- Cited by
- 531
- References
- 61
- FWCI
- 14.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
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