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

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.

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients

“…Diabetic patients treated with metformin showed a lower incidence of CRC (35)(36)(37) and mortality from CRC (38)(39)(40). In the present study, diabetic patients taking ASA and metformin have both higher five-year cancer-specific and relative survival for stage II and III CRC compared with diabetic patients not taking ASA and to nondiabetic patients with or without ASA intake.…”

Metformin: Hype or Hope for Cancer

“…26 Metformin use -after pancreatic cancer operation-resulted in a median survival of 35.5 months 27 In colorectal carcinoma, metformin caused 44% reduction in all-cause mortality and 34% in risk of mortality. 28 In colon cancer cells, metformin was demonstrated to increase apoptosis in p53 deficient cells. 29 In postmenopausal women with diabetes, metformin was found to have protective effect on breast cancer risk (OR 0.83, 95% CI 0.71-0.97).…”

Uso de metformina e a ocorrência de neoplasias em pacientes com Diabetes Mellitus pré-existente

“…Um crescente número de estudos tem identificado pacientes com diabetes como tendo um risco aumentado para o desenvolvimento do câncer (SORANNA et al, 2012;RIZOS E ELIZAF, 2013;CHUNG et al, 2013;FRANCIOSI et al, 2013;BADRICK e RENEHAN, 2014;LI e KONG, 2014;MEI et al, 2014;GU et al, 2015).…”

“…Além disto, a própria hiperglicemia parece favorecer a carcinogênese (SORANNA et al, 2012). Evidências epidemiológicas sugerem que, além do risco aumentado de desenvolver a doença, o diabetes está associado ao aumento da mortalidade específica por câncer (PARK, 2013;MALEK et al, 2013;MEI et al, 2014).…”

“…A insulina pode influenciar tumorigênese diretamente, agindo sobre a insulina/fatores de crescimento semelhantes à insulina ou indiretamente influenciando outros moduladores, tais como os hormônios sexuais, fatores de crescimento semelhantes à insulina e adipocinas (FRANCIOSI et al, 2013). Mei et al (2014), relata que vários fatores de risco são compartilhados por diabetes e câncer, tais como obesidade, maus hábitos alimentares, tabagismo.…”