Metformin is associated with survival benefit in pancreatic cancer patients with diabetes: a systematic review and meta-analysis

Abstract

Background: Pancreatic cancer is a highly lethal disease with a poor prognosis while metformin has been associated with a decreased risk of pancreatic cancer. Although the benefit of metformin was observed for pancreatic cancer prevention, it is not clear whether it can also affect the survival of pancreatic cancer patients with type 2 diabetes mellitus. A systematic review and meta-analysis was conducted to assess the effect of metformin on the survival of pancreatic cancer patients with type 2 diabetes mellitus.

Methods: Two independent authors searched PubMed and Web of science up to 08/07/2016. We assessed studies for eligibility, extracted data, and examined their quality, with the primary outcome as overall survival. We used published hazard ratio (HR) available or estimated based on other survival data. We pooled the data and used a random-effect model to combine direct comparisons from included articles. We also investigated treatment effects by different countries, quality and the time of metformin initiation.

Results: We found that there was a relative survival benefit associated with metformin treatment compared with non-metformin treatment in both overall survival (OS) ([HR] 0.84; 95% confidence interval [CI]: 0.73 - 0.96). These associations were also observed in subgroups of Asian countries and high quality articles.

Conclusions: Our results support the notion that metformin maybe the best anti-diabetic medicine of choice in patients with pancreatic cancer and concurrent type 2 diabetes mellitus. The perspectives of enhancing survival of pancreatic cancer patients with diabetes mellitus by the use of metformin deserve more attention in future research and clinical practice.

Keywords: diabetes; metformin; overall survival; pancreatic cancer.

Figure 1. Flow diagram of study identification

Figure 2. Forest plot (random effects model) of pooled Hazard ratios(HRs) of overall survival by metformin versus non-metformin treatment

Each study is shown by the point estimate of the HR (the size of the square is proportional to the weight of each study) and 95% CI for the HR (extending lines). The diamond represents the summary HR and 95% CI.

Figure 3. Funnel Plots to detect publication bias

Each circle represents an individual article. HR indicates Hazard ratio. Circle represents identified studies.