Association between metformin use after surgery for colorectal cancer and oncological outcomes: A nationwide register‐based study

Abstract

Colorectal cancer is one of the most common malignancies in the Western world, and even after surgical removal, there is a high recurrence rate. Metformin treatment has been associated with a reduced risk of developing cancer, but whether metformin influences the risk of recurrence is unknown. The aim of our study was to examine the association between treatment with metformin and recurrence-free, disease-free survival and all-cause mortality after surgery for colorectal cancer. The study was an observational register-based study and included 25,785 patients, of which 1,116 had medically treated diabetes and 966 started metformin treatment at some point postoperatively. Diabetes was not associated with neither disease-free (HR = 1.09, 95% CI 0.97-1.21, p = 0.15) nor recurrence-free survival (HR = 1.13, 95% CI 0.95-1.35, p = 0.17). The study found no difference in regards to disease-free or recurrence-free survival between the metformin treated group (HR = 1.06, 95% CI 0.87-1.15, p = 0.57, HR = 1.01, 95% CI 0.89-1.15, p = 0.85) and non-diabetic patients. Patients with diabetes had increased all-cause mortality (HR = 1.29, 95% CI 1.16-1.45, p < 0.0001). Metformin treatment did not affect all-cause mortality (HR = 1.07, 95% CI 0.94-1.22, p = 0.33) compared to non-diabetic patients. In conclusion, our study did not find an association between diabetes or metformin treatment and recurrence-free or disease-free survival after surgery for colorectal cancer. However, diagnosis of diabetes is associated with increased all-cause mortality.

Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling

“…Metformin, an oral biguanide agent that was FDA-approved in 1957, has been used as a safe and cost-efficient treatment for T2D worldwide (45,46). Numerous studies have indicated that long-term administration of metformin reduces the risk of various types of cancer, including breast, colon and endometrial cancer, and glioma (13-17,20,47). Recently, Li et al (48) demonstrated that metformin can increase the survival rate of diabetic patients with gastric cancer.…”

“…The epidemiological studies have suggested that the use of metformin is associated with a decreased incidence of cancer, and improved prognosis and cancer-associated mortality in patients with T2D (13,14). The anticancer effects of metformin have been reported in breast (15,16), colorectal (17), liver (18), cervical (19), endometrial (20), gastric (21), lung (22), ovarian (23), prostate (24), pancreatic (25) and renal (26) cancer. Various studies have demonstrated that the anticancer mechanisms of metformin are mediated via the AMPK/mammalian target of rapamycin (mTOR) cascade, and the signaling is dependent on AMPK activation leading to inhibition of mTOR that represses protein synthesis, cell proliferation, cell cycle progression and apoptotic cell death (27-29).…”

A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction among Individuals with History of Colorectal Adenomas and Elevated Body Mass Index

“…Although agreement in the literature is not uniform (10,11), a growing evidence base of population-based studies (12)(13)(14)(15)(16)(17) shows reduced cancer (including colorectal cancer; refs. 18,19) incidence and cancer-specific death among diabetics using metformin versus other treatments.…”

Metformin Treatment for Diabetes Mellitus Correlates with Progression and Survival in Colorectal Carcinoma

“…Other studies which attempted to avoid the potential confounders of adjuvant therapy, focused more on stratified patients by TNM stage, did not show any effect of metformin on the course of CRC. Recent prospective studies suggested at least a 15% decrease in risk of all-cause mortality in CRC patients with T2DM treated with metformin compared with patients receiving insulin [[23], [24], [25], [26]].…”