By Seema Gupta, MD, MSPH
Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine,
Marshall University, Huntington, WV
Dr. Gupta reports no financial relationships relevant to this field of study.
SYNOPSIS: In a retrospective cohort study of patients with type 2 diabetes who had ≥ 1 adenoma detected at baseline colonoscopy and a repeat colonoscopy 1-10 years later, metformin use lowered the risk of subsequent adenomas after polypectomy.
SOURCE: Marks AR, et al. Metformin use and risk of colorectal adenoma after polypectomy in patients with type 2 diabetes mellitus. Cancer Epidemiol Biomarkers Prev 2015;24:1692-1698.
An insulin sensitizing drug, metformin acts directly against insulin resistance and is regarded as the most commonly prescribed drug for the prevention or treatment of type 2 diabetes mellitus worldwide. Metformin, compared with other antidiabetic drugs, has been associated with cancer risk reduction in recent epidemiologic studies in diabetic patients.1 The use of metformin in diabetic patients also has been associated with significantly lower risks of cancer mortality and incidence.2 These analyses in patients with diabetes have found an association between metformin use and reductions in the incidence of pancreatic, liver, breast, and colorectal cancers with varying levels of statistical significance.3 However, not all studies have found such a relationship.4
While colorectal cancer is the second-leading cause of cancer-related death in the United States, there remains a paucity of literature on the association of metformin use and the risk of developing colorectal adenoma. Furthermore, since many patients develop subsequent adenomas after initial polypectomy, there have been no studies examining the effect of metformin in reducing the risk of adenoma redevelopment.
Marks et al examined the relationship between metformin use and detection of new or recurrent adenomas at follow-up examination after polypectomy in patients with type 2 diabetes. Researchers conducted a retrospective cohort study of type 2 diabetes patients who were between 40 and 89 years of age. All study participants also had at least one colorectal adenoma identified at baseline colonoscopy, and at least one colorectal adenoma remaining through repeat colonoscopy up to 10 years from the baseline colonoscopy diagnosis of adenoma. The study included 2412 patients who were followed for a median of 4.5 years. Overall, 1117 (46%) patients were found to have at least one adenoma during repeat colonoscopy after the discovery of the baseline adenoma. Compared with patients not receiving diabetes medications (n = 1578), metformin-only patients (n = 457) were associated with lower adenoma recurrence risk (adjusted hazard ratio, 0.76; 95% confidence interval [CI], 0.65-0.89). Furthermore, the association between lower adenoma incidence and metformin use improved with higher total doses of metformin.
COMMENTARY
This study suggests a potential benefit of metformin use in lowering the risk of subsequent adenomas after polypectomy in patients with type 2 diabetes when compared with no diabetes therapy. Pre-cancerous adenomas are the most common cause of colorectal cancer. This finding suggests metformin use may confer additional benefits in lowering the risk of adenoma. There are a number of postulated mechanisms for such a benefit, including the inhibition of mechanistic target of rapamycin (mTOR) pathway and insulin-like growth factor signaling suppression.5 However, while there is the potential for both direct antitumor effects and indirect host-mediated effects, it is important to await further research from clinical trials of metformin as an anticancer agent in the clinical setting prior to recommending it for cancer chemoprevention. It is, however, comforting to know that there may be additional benefits to an older medication, which convincingly remains the cornerstone in the management of a common disease — type 2 diabetes.
REFERENCES
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Bodmer M, et al. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care 2010;33:1304-1308.
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Noto H, et al. Cancer risk in diabetic patients treated with metformin: A systematic review and meta-analysis. PLoS One 2012;7:e33411.
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Decensi A, et al. Metformin and cancer risk in diabetic patients: A systematic review and meta-analysis. Cancer Prev Res (Phila) 2010;3:1451-1461.
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Kowall B, et al. No reduced risk of overall, colorectal, lung, breast, and prostate cancer with metformin therapy in diabetic patients: Database analyses from Germany and the UK. Pharmacoepidemiol Drug Saf 2015;24:865-874.
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Pollak MN. Investigating metformin for cancer prevention and treatment: The end of the beginning. Cancer Discov 2012;2:778-790.
