Metformin and Cancer: Solutions to a Real-World Evidence Failure
| العنوان: | Metformin and Cancer: Solutions to a Real-World Evidence Failure |
|---|---|
| المؤلفون: | Oriana Hoi Yun Yu, Samy Suissa |
| المصدر: | Diabetes Care. 46:904-912 |
| بيانات النشر: | American Diabetes Association, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Advanced and Specialized Nursing, Endocrinology, Diabetes and Metabolism, Internal Medicine |
| الوصف: | The quest to repurpose metformin, an antidiabetes drug, as an agent for cancer prevention and treatment, which began in 2005 with an observational study that reported a reduction in cancer incidence among metformin users, generated extensive experimental, observational, and clinical research. Experimental studies revealed that metformin has anticancer effects via various pathways, potentially inhibiting cancer cell proliferation. Concurrently, multiple nonrandomized observational studies reported remarkable reductions in cancer incidence and outcomes with metformin use. However, these studies were shown, in 2012, to be affected by time-related biases, such as immortal time bias, which tend to greatly exaggerate the benefit of a drug. The observational studies that avoided these biases did not find an association. Subsequently, the randomized trials of metformin for the treatment of type 2 diabetes and as adjuvant therapy for the treatment of various cancers, advanced or metastatic, did not find reductions in cancer incidence or outcomes. Most recently, the largest phase 3 randomized trial of metformin as adjuvant therapy for breast cancer, which enrolled 3,649 women with a 5-year follow-up, found no benefit for disease-free survival or overall survival with metformin. This major failure of observational real-world evidence studies in correctly assessing the effects of metformin on cancer incidence and outcomes was caused by preventable biases which, surprisingly, are still prominent in 2022. Rigorous approaches for observational studies that emulate randomized trials, such as the incident and prevalent new-user designs along with propensity scores, avoid these biases and can provide more accurate real-world evidence for the repurposing of drugs such as metformin. |
| تدمد: | 1935-5548 0149-5992 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::ed496ab04dcbfba4a1edc1ce6deca143Test https://doi.org/10.2337/dci22-0047Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi...........ed496ab04dcbfba4a1edc1ce6deca143 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19355548 01495992 |
|---|