Metformin anticancer activity
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Date
2017-06
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Addis Ababa Universty
Abstract
Background: Accumulating evidence suggests that patients with type 2 diabetes mellitus (T2DM) and hyperinsulinemia are at increased risk for developing malignancies. It remains to be fully elucidated whether use of metformin, an insulin sensitizer, and/or sulfonylureas (SUs), insulin secretagogues, affect cancer incidence in subjects with T2DM.
Objective: A meta-analysis was performed to compare the risk of cancer incidence associated with monotherapy with SUs versus monotherapy with metformin in T2DM patients.
Material and Methods: Search was performed throughout MedLINE/PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov up to April 30, 2012. Fixed- and random-effect models basing on heterogeneity were fitted to estimate the summary relative risk (RR). Between studies heterogeneity was tested using X2 statistics and measured with the I2 statistic. Publication bias was evaluated using funnel plot and Egger’s regression asymmetry test.
Results: A total of 10 studies, all of them were cohort studies, included in the meta-analysis. Obvious heterogeneity was noted, and Pooling of the raw data of those 10 cohort studies suggested that T2DM patients using SUs compared with metformin use had a significantly higher risk of overall cancer (RR= 1.59, 95% CI 1.38-1.83, I2=94.88%, p< 0.00001), using the random-effects model. But, after pooling of the adjusted estimates, the use of SUs was not associated with a higher cancer risk than metformin treatment (RR=1.12, 95% CI 1.05–1.19, I2=51.20%, p< 0.000145), using the random-effects model.
Conclusions and Recommendations: This analysis clearly shows that monotherapy with SUs can increase cancer risk compared to metformin monotherapy in T2DM patients. The evidence is not yet adequate to establish the effect of SUs, relative to metformin on cancer. Future investigators should consider more rigorous study design and data analysis, and use data with acceptable rigor. These findings need to be confirmed in large-scale RCTs before they are translated into clinical practice.
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metformin