Effects of metformin on survival outcomes of pancreatic cancer patients with diabetes: A meta-analysis

Abstract

Abstract. Pancreatic cancer risk is reduced by metformin treatment in patients with diabetes. However, the effect of metformin on pancreatic cancer overall survival is unclear. The aim of the present study was to determine the association between metformin and clinical outcomes of pancreatic cancer patients with diabetes. An electronic and manual search was conducted using PubMed, Web of Science, Medline-Ovid and Cochrane Library databases between the beginning and March 31, 2017. A total of 8 studies consisting of 4,293 patients with pancreatic cancer with diabetes were included, comprising 2,033 patients who had received metformin and 2,260 patients who had not. The meta-analysis showed that metformin was associated with a relative survival benefit in pancreatic cancer patients [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70-0.93]. These associations were also observed in subgroups of Asian countries 0.64 (95% CI, 0.52-0.80) and Western countries 0.88 (95% CI, 0.82-0.95), as well as diabetes (no indication of diabetes type). Excluding the studies considered as be prone to immortal time bias resulted in HRs (95% CIs) of 0.86 (0.69-1.07). The results of this study support the notion that the use of metformin may improve the overall survival of patients with pancreatic cancer with concurrent diabetes. However, the proposed beneficial effect of metformin on pancreatic cancer survival may be based on immortal time bias. Further carefully designed studies with high quality are warranted to confirm this efficacy.

Impact of metformin use on the outcomes of newly diagnosed diffuse large B‐cell lymphoma and follicular lymphoma

“…Multiple studies have suggested that metformin use was associated with lower incidences of various solid tumours such as pancreatic, colorectal, gastric, lung and breast cancer (Gandini et al, 2014;Wang et al, 2014;Zhu et al, 2015;Shlomai et al, 2016;Kobiela et al, 2018;Li et al, 2018b). There is also accumulating evidence that supports an association of metformin use with improved outcome of several types of solid tumours (Chu et al, 2018;Hu et al, 2018;Kobiela et al, 2018;Li et al, 2018b;Tang et al, 2018;Xin et al, 2018). There are fewer studies available regarding the role of metformin in haematological malignancies.…”

Repurposing old drugs in oncology: Opportunities with clinical and regulatory challenges ahead

“…In contrast, the same study found that the use of sulphonylureas or insulin was associated with 1.49‐ (95% CI: 1.00‐2.23) and 2.58‐fold (95% CI: 1.72‐3.90) higher risks of breast cancer death. Other recent meta‐analyses have also reported a beneficial effect of metformin on incidence and/or survival in various cancers including liver, prostate cancer, colorectal cancer, endometrial cancer and pancreatic cancer …”

“…Other recent meta-analyses have also reported a beneficial effect of metformin on incidence and/or survival in various cancers including liver, 54,55 prostate cancer, 56 colorectal cancer, 57,58 endometrial cancer 59,60 and pancreatic cancer. 61 Although some observational studies show clear evidence of survival benefit in cancer patients with diabetes receiving metformin, the situation is by no means clear. The complexity of the available evidence is illustrated by observational studies with negative findings.…”

Phenotypic functional activities of monocyte change during crosstalk with breast cancer cell and enhancing effect of metformin of IFN-γ-associated antitumor cytokine production

“…The anti-tumorigenic properties of MET have been reported in several studies associated with indirect action (reduced insulin levels) or direct actions on molecular pathways that regulate breast tumor cell growth and death (36). MET may mediate its effects through actions on different cells of the tumor microenvironment, including MOs-macrophages that would be involved in controlling tumor cell growth and progression.…”