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Metformin Thera..

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Type 2 diabetes has been associated with an increased risk of colorectal cancer, which is documented as one of the most common malignant tumors.1-2 Metformin, a biguanide, is the first-line drug of choice in most patients for the management of type 2 diabetes. Metformin has been shown in in vitro studies to inhibit cancer cell proliferation and selectively kill cancer cells, suggesting that this agent may reduce the risk of some malignancies.3-5 Due to limited and inconsistent data on metformin’s effect on colorectal cancer, Zhang and colleagues sought to examine the association between metformin therapy and colorectal cancer in patients with type 2 diabetes.3

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Zhang and colleagues conducted a meta-analysis of retrospective, observational studies that investigated the effect of metformin on colorectal cancer. The analysis included five studies, including two case-control studies and three retrospective cohort studies, comprising a total of 108,161 patients with type 2 diabetes. The relative risk (RR) was utilized as the common measure of association across studies. The RRs of each study were averaged to derive a pooled RR of colorectal cancer in type 2 diabetic patients receiving metformin therapy compared to those receiving nonmetformin therapies. The results of the analysis illustrated that metformin was associated with a significantly lower risk of colorectal neoplasm when compared to nonmetformin therapies (pooled RR 0.63, P < 0.001). Even after one small case-controlled study (n = 200) that specifically investigated colorectal adenoma was excluded from the analysis, metformin was still associated with a lower risk of colorectal cancer when compared to nonmetformin therapies (RR 0.63, P = 0.002). The authors concluded that metformin appears to be associated with a significantly lower risk of colorectal cancer in patients with type 2 diabetes. The authors did note that further investigation was warranted.3

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This meta-analysis found that metformin appears to be associated with a significantly lower risk of colorectal cancer in patients with type 2 diabetes. However, this analysis is not without limitations. Ioannou and Boyko call attention to the fact that as a meta-analysis of observational studies, not of randomized controlled trials, this analysis inherits all the limitations that exist in the original observational studies. This includes potential for incomplete adjustment for confounding and follow-up time of the studies included in the meta-analysis.6 An additional limitation of this analysis is that metformin therapy was compared with all nonmetformin therapies, including insulin and oral therapies. Previous studies have revealed conflicting data that insulin therapy may or may not increase the risk of colorectal cancer in patients with type 2 diabetes.7-9 In addition to insulin therapy, sulfonylureas have been linked to an increased risk of cancer-related mortality.8 Sulfonylureas are typically used as second-line agents in the management of type 2 diabetes, often in combination with metformin therapy. Therefore, any protective benefits provided by metformin therapy may have been secondary to harmful effects of the nonmetformin therapies. As mentioned previously, metformin is already the first-line drug of choice in most patients for the management of type 2 diabetes. Thus, the findings of this analysis should have no clinical implications on the management of patients with type 2 diabetes. However, future research regarding this topic should include a well-designed randomized controlled ...

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