Metformin and the Risk of Cancer

作者：Samy Suissa, Laurent Azoulay · 发表于：Diabetes Care · 年份：2012 · DOI：10.2337/dc12-0788 · 被引用次数：535 · 研究领域：Metabolism, Diabetes, and Cancer、Cancer Risks and Factors、Cancer, Lipids, and Metabolism

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 underst...