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Can Metformin Prevent Colorectal Cancer for Type 2 Patients?

Meta-analysis found metformin therapy was associated with decreased risk for colorectal adenomas and colorectal cancer among T2 patients.

Studies have suggested that patients with type 2 diabetes may be at an increased risk for developing colorectal cancer (CRC); hyperinsulinemia, hyperglycemia, and chronic inflammation are thought to all contribute to carcinogenesis. Metformin, a biguanide, exerts its antihyperglycemic effects by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. Being that metformin is the most commonly prescribed medication for the treatment of type 2 diabetes, researchers sought to assess whether metformin use has an effect on the incidence of CRC in this patient population. A total of 8,046 study participants were included in the analysis (2,682 in the case group [diabetes patients with incident diagnosis of CRC]; 5364 individuals in the control group [diabetic patients without CRC diagnosis]); each group was 60% male, 40% female. In the case group, 36.6% of patients had metformin exposure, while 38.4% had metformin exposure in the control group. In this study, any metformin use led to a 15% reduction in the odds of CRC; after accounting for healthcare use, the effect was reduced to 12%. Reduction of risk was not significantly associated with metformin dose, duration or total exposure.

Metformin therapy was associated with decreased incidence of colorectal adenomas (P=.0002).  On adjusted analysis, the summary estimate decreased further to a 25% reduction in colorectal adenoma risk (P=.03).  Colorectal cancer risk was also significantly reduced among metformin users vs metformin non-users or other treatment users (P=.0002).  Adjusted analysis revealed a 22% reduction in colorectal cancer risk for metformin users (P<.00001).

Recent evidence indicates that metformin therapy may be associated with a decreased colorectal adenoma/colorectal cancer risk in type 2 diabetes patients. However, results are not consistent. So a systematic review and meta-analysis to assess the association between metformin therapy and risk of colorectal adenomas/colorectal cancer in type 2 diabetes mellitus patients was done. They searched the literature published before Aug. 31, 2016 in four databases: PubMed, Embase database, CNKI and VIP Library of Chinese Journal. Summary risk estimates with their 95% confidence interval (95% CI) were obtained using a random effects model. Twenty studies (including 12 cohort studies, 7 case-control studies and 1 randomized controlled trial study) were selected in terms of data of colorectal adenomas or colorectal cancer incidence. Metformin therapy was found to be associated with a decreased incidence of colorectal adenomas (p=0.0002). When the adjusted data were analyzed, the summary estimate decreased to 25% reduction in colorectal adenomas risk (p=0.03). Besides, a significant reduction of colorectal cancer risk was also observed (p=0.0002). And when the adjusted data were analyzed, colorectal cancer risk for metformin users was decreased with a reduction of 22%, compared with non-metformin users and other treatment users  (p<0.00001).

In another study published in Cancer in 2014, it was also concluded that metformin use appears to be associated with a reduced risk of developing CRC among diabetes patients in the United States by 12%. The mean age of the study participants was 55 years and 57 years, respectively, in the control and case groups (P = 1.0). Approximately 60% of the study participants were male and 40% were female in each group. In the multivariable model, any metformin use was associated with a 15% reduction in the odds of CRC. The dose-response analyses demonstrated no significant association with metformin dose, duration, or total exposure.

From the results of multiple studies, it was concluded that the meta-analysis suggested that metformin therapy may be associated with a decreased risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients.

Practice Pearls:

  • Metformin over the years has been the first recommended medication for patients with type 2 diabetes, with very few side effects.
  • Patients with diabetes have been shown to be at greater risk for cancer.
  • Metformin therapy may be associated with a decreased risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients.

Oncotarget. 2016 Dec 1. doi: 10.18632/oncotarget.13762; Cancer 2015;121:1071–1078. © 2014 American Cancer Society.

Published in Cardiology  December 21, 2016 Journal of the American College of Cardiology