Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer

Garrett, Christopher R.; Hassabo, Hesham M.; Bhadkamkar, Nishin A.; Wen, Sijin; Baladandayuthapani, V; Kee, Bryan K.; Eng, Cathy; Hassan, Manal M.

doi:10.1038/bjc.2012.71

Cited by 133 publications

(133 citation statements)

References 31 publications

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“…In a separate analysis of 212 postmenopausal women with colorectal cancer and type 2 diabetes, no statistically significant difference in colorectal cancer-specific survival was observed among users of metformin compared to non-users (HR 0.75, 95% CI 0.40-1.38) although unfortunately, the authors of this study were unable to obtain data on the timing of metformin use in relation to colorectal cancer diagnosis. 28 Other epidemiological studies investigating metformin use after colorectal cancer diagnosis and all-cause mortality and have indicated a beneficial effect with metformin use, 11,12 however these investigations are limited by small sample size and the use of only one exposure timepoint. Moreover, findings from studies which only examine the impact of metformin on all-cause mortality may be reflective of non-cancer mortality.…”

Section: Discussionmentioning

confidence: 99%

Metformin use and survival after colorectal cancer: A population‐based cohort study

McMenamin¹,

Murray²,

Hughes

et al. 2015

Intl Journal of Cancer

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Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metformin and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use and cancer-specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancerspecific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other antidiabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.Despite advances in surgical techniques and adjuvant therapies, colorectal cancer remains the third leading cause of cancer death. 1 Preclinical evidence suggests a beneficial role for metformin, a first-line oral anti-diabetic agent, in colorectal cancer progression. [2][3][4] Although not fully elucidated, the potential anti-tumour effects of metformin are thought to be due to inhibition of the mammalian target of rapamycin (mTOR) signalling pathway, resulting in suppression of cellular proliferation 5 tumour cell migration and invasion 6 as well as an increase in apoptosis. 7 Despite mounting preclinical evidence supporting a possible therapeutic role for metformin in colorectal cancer, only two epidemiological studies have evaluated the impact of post-diagnostic metformin exposure on cancer outcomes in colorectal cancer patients with type 2 diabetes. A Korean study of 595 colorectal cancer patients with type 2 diabetes reported substantial reductions in risk of colorectal cancerspecific and all-cause mortality among metformin users after diagnosis. 8 However, individuals in this study were improperly classified as exposed to metformin in the period from cohort entry to first metformin prescription and therefore these findings have been attri...

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Section: Discussionmentioning

confidence: 99%

Metformin use and survival after colorectal cancer: A population‐based cohort study

McMenamin¹,

Murray²,

Hughes

et al. 2015

Intl Journal of Cancer

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“…Although strong evidence supports the association of diabetes with crc, and recent work has examined metformin as a prognostic factor in crc, results are contradictory and tend to be related to specific patient populations [15][16][17][18][19] . In the present retrospective study, we set out to investigate whether metformin use in diabetic patients diagnosed with crc was associated with survival.…”

Section: Introductionmentioning

confidence: 99%

A Retrospective Study on the Role of Diabetes and Metformin in Colorectal Cancer Disease Survival

et al. 2016

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“…Metformin use has been associated with improved survival in patients with diabetes with breast [2], colorectal [3] and prostate cancer [4]; however there are limited data in lung cancer patients. Constitutive mTOR signaling plays an important role in the development of lung cancer and in vitro and animal studies have reported antiproliferative effects [5] and proapoptotic effects [6], as well as the inhibition of lung tumour growth [7].…”

Section: Introductionmentioning

confidence: 99%

Metformin use and survival from lung cancer: A population-based cohort study

et al. 2016

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word count: 222 Manuscript word count: 1,472Number of tables and figures: 2 Abbreviations: BMI, body mass index; CIs, confidence intervals; CPRD, Clinical Practice Research Datalink; DDD, daily defined dose; GP, general practitioner; HR, hazard ratio; NCDR, National cancer Data Repository; ONS, Office of National Statistics; UK, United Kingdom; WHO, World Health Organisation. AbstractPreclinical evidence suggests that metformin, a widely prescribed anti-diabetic drug, may inhibit lung cancer progression. We investigated whether metformin use was associated with decreased risk of cancer-specific mortality in lung cancer patients. This study included newly diagnosed lung cancer patients (identified from English National Cancer Data Repository, 1998-2009) with type 2 diabetes (based on UK Clinical Practice Research Datalink prescriptions and diagnosis records). Lung cancer deaths occurring up to 2012 were identified using Office of National Statistics mortality data and the association between metformin use (before and after diagnosis) and risk of lung cancer-specific mortality was calculated using Cox regression models. In analysis of 533 patients, we found a weak non-significant reduction in lung cancer-specific mortality with metformin use after diagnosis (adjusted HR, 0.86; 95% CI, 0.68-1.09). No association was evident for metformin use before diagnosis and cancer-specific mortality in analysis of 1,350 patients (adjusted HR, 0.97; 95% CI, 0.86, 1.11). Associations were similar by duration of use. In addition, after adjustment for potential confounders, there was little evidence of an association between the use of other anti-diabetic medications (either before or after diagnosis) and lung cancer-specific mortality; including sulfonylureas, insulin or other anti-diabetic medications (such as thiazolidinediones). Overall, the results from this population-based study provide little evidence of a protective association between metformin use and cancer mortality in lung cancer patients.

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Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer

Cited by 133 publications

References 31 publications

Metformin use and survival after colorectal cancer: A population‐based cohort study

Metformin use and survival after colorectal cancer: A population‐based cohort study

A Retrospective Study on the Role of Diabetes and Metformin in Colorectal Cancer Disease Survival

Metformin use and survival from lung cancer: A population-based cohort study

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