Prognostic role of metformin intake in diabetic patients with colorectal cancer: An updated qualitative evidence of cohort studies

Abstract

Several observational studies have shown that metformin can modify the risk and survival of colorectal cancer (CRC) in patients with diabetes mellitus, although the magnitude of this relationship has not been determined. We conducted an updated systematic review and meta-analysis to analyze the association between metformin and CRC mortality and searched relevant databases up to July 2016. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CS) and disease-free survival (DFS). Summary hazard ratios (HRs) were calculated using a random-effects model. Seventeen studies enrolling 269,417 participants were eligible for inclusion. Comparing with non-metformin users in diabetic CRC patients, the summary HRs for OS in metformin users were 0.69 (95% CI, 0.61-0.77). Subgroup analyses stratified by the study characteristics and sensitivity analysis by the trim-and-fill method (adjusted HR 0.77, 95% CI, 0.67-0.87) confirmed the robustness of the results. However, significant OS benefit was noted in patients with stage II and III disease. Five studies reported the CRC prognosis for CS and three for DFS; metformin intake was significantly associated with patient CS (HR 0.75, 95% CI, 0.59-0.94), but not DFS (HR 0.38, 95% CI, 0.13-1.17). Our findings suggest that metformin intake is associated with improved survival outcomes in terms of OS and CS in CRC patients with diabetes, particular for OS in stage II and stage III patients. Further studies should be conducted to determine CRC survival between metformin use and patient specific clinical and molecular profiles.

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

“…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. These results differ from those obtained by Mei et al (38), Du et al (39) and Ramjeesingh et al (40) who showed the protective effect of metformin on CRC patient mortality. On the other hand, Zanders and colleagues (41) did not find any survival improvement in CRC patients taking metformin or ASA.…”

“…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.…”

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

“…Data concerning potential uses of metformin as an adjuvant treatment in patients who have already developed colorectal cancer are even more scarce: while a series of published papers suggest that metformin use might be associated with improved survival [ 85 , 86 , 87 , 88 ], in all these studies, the number of patients with unresected metastatic disease is rather low (usually lower than 3–4% of the whole patient population).…”

Multidimensional effects of metformin in patients with type 2 diabetes

“…При анализе семнадцати наблюдательных исследований (n=269 417) Du L. et al (2017) показали, что метформин может модифицировать риск и выжива-ние при колоректальном раке [63], хотя требуется уточне-ние клинических и молекулярных профилей пациентов. Мета-анализ 17 исследований в 10 публикациях показал, что применение метформина было в значительной сте-пени связано с благоприятным исходом выживаемости больных раком легкого с диабетом, получавших химио-терапию, но не в сочетании с лучевой терапией [64].…”