Postdiagnostic metformin use and survival of patients with colorectal cancer: A Nationwide cohort study

Huang, Wen‐Shih; Chang, Shu‐Hao; Hsu, Hung‐Chih; Chou, Wen‐Chi; Yang, Tsung‐Ming; Chen, Jen‐Shi; Chang, John Wen‐Cheng; Lin, Yung‐Chang; Kuo, Chang‐Fu; See, Lai‐Chu

doi:10.1002/ijc.32989

Cited by 11 publications

(9 citation statements)

References 146 publications

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“…Our epidemiological study was one of the first to focus solely on RC in the general diabetic population, and we did not find convincing evidence about the association between metformin use, either pre-diagnostic or post-diagnostic, and reduced mortality from RC. A similar result was observed in a previous study analyzing post-diagnostic use and RC mortality [ 32 ]. Additionally, a trend toward lower association, especially in women, has been reported [ 33 ], and higher metformin adherence has been previously associated with lower RC mortality when compared to low adherence [ 34 ].…”

Section: Discussionsupporting

confidence: 90%

The Association of Metformin, Other Antidiabetic Medications and Statins on the Prognosis of Rectal Cancer in Patients with Type 2 Diabetes: A Retrospective Cohort Study

et al. 2022

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Metformin and statin use have been associated with an improved prognosis for colorectal cancer in persons with type 2 diabetes (T2D). Data regarding rectal cancer (RC) have been inconclusive; therefore, we investigated the issue with high-quality data and a robust study design. We identified 1271 eligible patients with T2D and incident RC between 1998 and 2011 from the Diabetes in Finland (FinDM) database. Cox models were fitted for cause-specific mortality rates to obtain adjusted estimates of the hazard ratios (HR) with 95% confidence intervals (CI) in relation to use of antidiabetic medication (ADM) and statins before the RC diagnosis and for post-diagnostic use in a time-dependent exposure manner. No sufficient evidence was found for either pre- or post-diagnostic metformin use and RC mortality (HR 0.96, 95% CI 0.67–1.38, and 0.70, 95% CI 0.45–1.10, respectively) when compared to other oral ADMs. Both pre- and post-diagnostic statin use appeared to be inversely associated with mortality from RC (HR 0.77 95% CI 0.63–0.94, and 0.57, 95% CI 0.42–0.78, respectively). Our study was inconclusive as to the association of metformin use with the prognosis of RC, but statin use was found to predict reduced mortality, both from RC and from other causes of death in persons with T2D.

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Section: Discussionsupporting

confidence: 90%

The Association of Metformin, Other Antidiabetic Medications and Statins on the Prognosis of Rectal Cancer in Patients with Type 2 Diabetes: A Retrospective Cohort Study

et al. 2022

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“… 33 The study group was similar to ours, although our classification also included stage I cases. Three other studies focusing on post-diagnostic use in all CC stages found either reduced cancer specific mortality, 34 reduced cancer specific mortality in women-only study 35 and no association in a study with similar methodology to ours. 36 A high metformin medication adherence has been associated with reduced cancer specific mortality when compared to low adherence.…”

Section: Discussionsupporting

confidence: 62%

The Association of Metformin, Other Antidiabetic Medications, and Statins With the Prognosis of Colon Cancer in Patients With Type 2 Diabetes: A Retrospective Cohort Study

et al. 2022

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Background Use of metformin and statins have been associated with improved prognosis of colon cancer (CC) in patients with type 2 diabetes (T2D). We examined the survival from CC in relation to the use of metformin, other oral antidiabetic medications (ADM), insulin, and statins in T2D patients. Materials and Methods A cohort (n = 2252) of persons with pre-existing T2D diagnosed with incident CC between 1998 and 2011 was identified from several Finnish registers. Cox models were fitted for cause-specific mortality rates to obtain adjusted estimates of the hazard ratios (HR) with 95% confidence intervals (CI) in relation to use of ADM and statins before the CC diagnosis. Cox models were also fitted for mortality in relation to post-diagnostic use of the medications treating these as time-dependent exposures, and starting follow-up 1 year after the CC diagnosis Results Pre- and post-diagnostic metformin use was weakly associated with the risk of CC–related death (HR .75; 95% CI .58-.99, and HR .78; 95% CI .54-1.14, respectively) compared to the use of other oral ADMs. Pre- and post-diagnostic statin use predicted a reduced risk of CC–related death (HR .83; 95% CI .71- .98, and HR .69; 95% CI .54-.89, respectively). Conclusion Additional evidence was found for use of statins being associated with an improved survival from CC in patients with pre-existing T2D, but for metformin use the evidence was weaker.

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“…CRC and diabetes mellitus share various clinical risk factors leading to an interest in anti-diabetic agents as potential chemopreventive drugs for CRC. Metformin, as the first-line oral medicine for type 2 diabetes, has been shown to significantly reduce colorectal adenoma and cancer incidence and improving survival outcomes ( 147 , 148 ). In the context of CRC, the protective effects of metformin are likely multi-factorial.…”

Section: Chemopreventive Drugsmentioning

confidence: 99%

Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges

Zhang

Qin

et al. 2021

Front. Oncol.

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Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.

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Postdiagnostic metformin use and survival of patients with colorectal cancer: A Nationwide cohort study

Abstract: The public defense of the dissertation will be held at the Marc Bygdeman Auditorium, BioClinicum J3:13, Solnavägen 30,

Cited by 11 publications

References 146 publications

The Association of Metformin, Other Antidiabetic Medications and Statins on the Prognosis of Rectal Cancer in Patients with Type 2 Diabetes: A Retrospective Cohort Study

The Association of Metformin, Other Antidiabetic Medications and Statins on the Prognosis of Rectal Cancer in Patients with Type 2 Diabetes: A Retrospective Cohort Study

The Association of Metformin, Other Antidiabetic Medications, and Statins With the Prognosis of Colon Cancer in Patients With Type 2 Diabetes: A Retrospective Cohort Study

Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges

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