Survival Benefits of Metformin for Colorectal Cancer Patients with Diabetes: A Systematic Review and Meta-Analysis

Zu-Bing Mei,Long Cui,Yun Liu,Ang Cui,Zhong-Lin Liang,Guang-Hui Wang,Zhi-Jiang Zhang,Chen-Ying Liu,Antonio Moschetta

doi:10.1371/journal.pone.0091818

Zu-Bing Mei, Long Cui + Show 7 more

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https://doi.org/10.1371/journal.pone.0091818

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Abstract

BackgroundSeveral studies suggest that metformin has the potential effect of reducing cancer risk. However, its survival benefit in patients with colorectal cancer (CRC) and diabetes is unknown. The aim of our study is to address the effect of metformin on outcomes for CRC based on a systematic review and meta-analysis.Methods and FindingsWe searched EMBASE and MEDLINE databases from inception through August, 2013, using search terms related to metformin, diabetes, colorectal cancer, and prognostic outcome. The outcome measures were hazard ratios (HRs) with 95% CIs comparing CRC survival in diabetic patients using metformin and without using metformin. The primary end points were overall survival (OS) and CRC specific survival (CS). A total of six cohort studies including 2,461 patients met full eligibility criteria. The pooled HR favoring metformin users was 0.56 for OS (95% CI, 0.41 to 0.77) and 0.66 for CRC-specific survival (95% CI, 0.50 to 0.87). Thus metformin therapy reduced the risk of all cause of death by 44% and the risk of CRC specific death by 34% in CRC patients compared to those in non-users. However, evidence of heterogeneity and possible publication bias was noted for OS.ConclusionsPatients with CRC and diabetes treated with metformin appear to have an improved survival outcome. Prospective study should be warranted to examine the association between metformin exposure intensity as well as some other confounding variables and survival outcome in diabetic CRC patients.

Highlights

Previous epidemiologic studies suggest that patients with type 2 diabetes have a conspicuous increase in cancer risk and mortality compared with non-diabetic counterpart [1,2,3,4,5,6]
Patients with colorectal cancer (CRC) and diabetes treated with metformin appear to have an improved survival outcome
Prospective study should be warranted to examine the association between metformin exposure intensity as well as some other confounding variables and survival outcome in diabetic CRC patients

Summary

Introduction

Previous epidemiologic studies suggest that patients with type 2 diabetes have a conspicuous increase in cancer risk and mortality compared with non-diabetic counterpart [1,2,3,4,5,6]. Diabetic patients with cancer have worse prognosis and an increased risk of death [10]. A first-line oral antidiabetic agent for type 2 diabetes, has been found to play a potential role in anticancer effect through molecular mechanisms of the ATM/LKB1/AMPK axis and mammalian target of rapamycin (mTOR)-signaling pathway [13]. The mTOR pathway regulates cell growth and tumorigenesis, and associates with tumor progression and prognosis. This role in CRC is mostly limited by observational population-based or clinic-based retrospective studies.

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