Metformin increases cancer specific survival in colorectal cancer patients—National cohort study

Dulskas, Audrius; Patašius, Aušvydas; Linkeviciute-Ulinskiene, Donata; Zabulienė, Lina; Urbonas, Vincas; Smailytė, Giedrė

doi:10.1016/j.canep.2019.101587

Cited by 31 publications

(28 citation statements)

References 18 publications

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“…Metformin is an oral ant hyperglycemic agent that has been used as first‐line treatment for type 2 DM for over 50 y. Numerous studies have suggested that metformin intake can significantly reduce the incidence of cancer development and mortality among patients with type 2 DM, although the degree of reduction varies among different types of cancer 8‐13 . However, the mechanisms underlying how metformin exerts this anti‐tumor effect is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Metformin changes the immune microenvironment of colorectal cancer in patients with type 2 diabetes mellitus

et al. 2020

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Accumulating evidence suggests that metformin reduces the incidence and mortality of colorectal cancer (CRC). However, underlying mechanisms have not been fully clarified. The aim of this study was to examine the pathological characteristics of resected CRC from patients treated with metformin for type 2 diabetes mellitus (DM). In total, 267 patients with DM underwent curative colectomy for Stage I‐III CRC and 53 (19.9%) patients had been treated medically including metformin. Pathological N‐stage was significantly lower in metformin‐treated patients (P < .05) with prolonged disease‐free survival (DFS) (P < .05). Immunohistochemistry showed that the densities of CD3(+) and CD8(+) tumor‐infiltrating lymphocytes (TILs) in the invasive front area were significantly higher in 40 patients treated with metformin compared with propensity score matched cases without metformin (P < .05). The density of tertiary lymphoid structures (TLS) in tumor stroma was markedly increased in metformin‐treated patients (P < .001). In those tumors, there were more CD68(+) tumor‐associated macrophages (TAM) infiltrated (P < .05), while the ratio of CD163(+) M2‐phenotype was markedly reduced (P < .001). Stromal fibrosis tended to be suppressed by metformin intake (P = .051). These findings suggested that metformin drastically changes the characteristics of infiltrating immune cells in CRC and reprograms the tumor microenvironment from immunosuppressive to immunocompetent status, which may lead to suppression of microscopic tumor spread and improve the outcomes of patients with CRC and type 2 DM.

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Section: Introductionmentioning

confidence: 99%

Metformin changes the immune microenvironment of colorectal cancer in patients with type 2 diabetes mellitus

et al. 2020

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“…Previously, we found that diabetic status had no effect on colorectal cancer specific and overall survival and, furthermore, antihyperglycemic treatment with metformin might have a positive effect on colorectal cancer by decreasing the incidence risk and prolonging the overall and cancer specific survival [12,13]. In another study, we showed that metformin might also have a positive effect on gastric cancer survival compared to other medication groups [14].…”

Section: Introductionmentioning

confidence: 84%

A Cohort Study of Antihyperglycemic Medication Exposure and Gastric Cancer Risk

Dulskas

Patašius

Kaceniene

et al. 2020

JCM

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We assessed gastric cancer risk in type 2 diabetes mellitus patients. Gastric cancer patients with diabetes between 2001–2012 were identified. Four groups were analysed: combination therapy with metformin users; insulin and other medication users; metformin and insulin users; and sulfonylurea users. Standardised incidence ratios (SIRs) for gastric cancers as a ratio of the observed number of cancer cases in people with diabetes to the expected number of cancer cases in the underlying general population were calculated. A total of 99,992 patients with diabetes were analysed and 337 gastric cancer cases in patients with diabetes were observed when compared to the expected number of 400.54 gastric cancer cases, according to the cancer rates of the general population (SIR 0.84, 95% confidence interval (CI): 0.76–0.94). Lower risk of gastric cancer was found both in male and female patients with diabetes, however, risk among females was insignificantly lower. Higher gastric cancer risk was found in the group of diabetic patients treated with sulfonylureas (SIR 1.31, 95% CI: 1.04–1.65) and significantly lower risk than expected from the general population was found in the group of metformin users (SIR 0.75, 95% CI: 0.66–0.86). Type 2 diabetes mellitus was not associated with increased risk of gastric cancer. Metformin might decrease the risk of gastric cancer in patients with diabetes, while sulfonylureas may increase gastric cancer risk.

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“…T2DM is a known risk factor for pancreatic cancer [ 2 ]. The pathophysiologic derangements that are responsible for the development of diabetes mellitus have also been associated with an increased risk for cancer development [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, metformin use has been associated with an improved survival of specific cancers, including colorectal, gastric, breast, and prostate cancers [ 23 , 24 , 25 , 26 ]. The effect of metformin on pancreatic cancer survival remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Cohort Study of Antihyperglycemic Medication and Pancreatic Cancer Patients Survival

Dulskas

Patašius

Linkeviciute-Ulinskiene

et al. 2020

IJERPH

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Background: We assessed the association between the use of metformin and other antihyperglycemic medications on overall survival in diabetic patients with pancreatic cancer. Methods: Patients with pancreatic cancer and diabetes between 2000 and 2015 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database. Cohort members were classified into six groups according to type 2 diabetes mellitus treatment: sulfonylurea monotherapy; metformin monotherapy; insulin monotherapy; metformin and sulfonylurea combination; metformin and other antihyperglycemic medications; all other combinations of oral antihyperglycemic medications. Survival was calculated from the date of cancer diagnosis to the date of death or the end of follow-up (31 December 2018). Results: Study group included 454 diabetic patients with pancreatic cancer. We found no statistically significant differences in overall survival between patients by glucose-lowering therapy. However, highest mortality risk was observed in patients on insulin monotherapy, and better survival was observed in the groups of patients using antihyperglycemic medication combinations, metformin alone, and metformin in combination with sulfonylurea. Analysis by cumulative dose of metformin showed significantly lower mortality risk in the highest cumulative dose category (HR 0.76, 95% CI 0.58–0.99). Conclusions: Our study showed that metformin might have a survival benefit for pancreatic cancer patients, suggesting a potentially available option for the treatment.

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Metformin increases cancer specific survival in colorectal cancer patients—National cohort study

Cited by 31 publications

References 18 publications

Metformin changes the immune microenvironment of colorectal cancer in patients with type 2 diabetes mellitus

Metformin changes the immune microenvironment of colorectal cancer in patients with type 2 diabetes mellitus

A Cohort Study of Antihyperglycemic Medication Exposure and Gastric Cancer Risk

Cohort Study of Antihyperglycemic Medication and Pancreatic Cancer Patients Survival

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