Metformin for primary colorectal cancer prevention in patients with diabetes: A case‐control study in a US population

Abstract

BACKGROUND: Emerging evidence from observational studies has suggested that metformin may be beneficial in the primary prevention of colorectal cancer (CRC). However, to the authors' knowledge, none of these studies was conducted in a US population. Because environmental factors such as Western diet and obesity are implicated in the causation of CRC, a large case-control study was performed to assess the effects of metformin on the incidence of CRC in a US population. METHODS: MarketScan databases were used to identify diabetic patients with CRC. A case was defined as having an incident diagnosis of CRC. Up to 2 controls matched for age, sex, and geographical region were selected for each case. Metformin exposure was assessed by prescription tracking within the 12-month period before the index date. Conditional logistic regression was used to adjust for multiple potential confounders and to calculate adjusted odds ratios (AORs). RESULTS: The mean age of the study participants was 55 years and 57 years, respectively, in the control and case groups (P 5 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 (AOR, 0.85; 95% confidence interval, 0.76-0.95 [P 5.007]). After adjusting for health care use, the beneficial effect of metformin was reduced to 12% (AOR, 0.88; 95% confidence interval, 0.77-1.00 [P 5.05]). The dose-response analyses demonstrated no significant association with metformin dose, duration, or total exposure. CONCLUSIONS: Metformin use appears to be associated with a reduced risk of developing CRC among diabetic patients in the United States.

Metformin and soybean-derived bioactive molecules attenuate the expansion of stem cell-like epithelial subpopulation and confer apoptotic sensitivity in human colon cancer cells

“…Clinical and epidemiological studies have implicated the anti-diabetic drug metformin (MET) in reducing the risk of CRC among diabetic patients as well as improving CRC outcome in patients with diabetes (Dowling et al 2011;Zhang et al 2013;Nangia-Makker et al 2014;Sehdev et al 2015). Additionally, in diabetic patients with CRC, the decrease in mortality with MET was inversely associated with the frequency of CD133 ?…”

“…Clinical studies suggest that MET treatment of diabetic patients reduces their risk of and mortality from CRC Sehdev et al 2015). The effects of MET on colon cancer proliferation and survival were investigated in HCT116 cells using MET at a near-physiological concentration of 60 lM (readily achievable in humans with daily doses of oral MET) (Ochs 2014).…”

“…The association between colonic intestinal proliferation and insulin is noteworthy, given that the anti-diabetic drug metformin (1,1-dimethylbiguanide hydrochloride; MET) has recently attracted much interest as a potential anticancer medication. Several epidemiological studies reported an inverse correlation between MET intake (at standard doses of 1500-2250 mg/day) and CRC incidence and related mortality in diabetic patients Sehdev et al 2015). Further, MET at a low dose (250 mg/day) was found to reduce colon epithelial cell proliferation and numbers of aberrant crypt foci in non-diabetic patients (Dowling et al 2011).…”

The Effect of Metformin on Colorectal Carcinoma in Type 2 Diabetes Mellitus Patients: A Markov Model Analysis

“…Some previous observational and mechanistic studies show positive results [35][36][37]. However, no demonstrable protective effect of metformin against malignancy is shown in the RCT (OR=0.69, 95% CI: 0.26-1.82) [23].…”

Metformin use and its effect on gastric cancer in patients with type 2 diabetes: A systematic review of observational studies

“…Metformin is easily accessed in clinical practice owing to its low-cost (2) and mild adverse drug reactions (3). The use of metformin has also been reported to reduce the risk of certain types of cancer in patients with type 2 diabetes mellitus (DM) (4)(5)(6)(7). Preclinical studies have indicated that metformin can inhibit the proliferation of cancer cells in vitro and in vivo (8), and simultaneously induce apoptosis (9).…”