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

// Ping-Ting Zhou 1, * , Bo Li 2, * , Fu-Rao Liu 1 , Mei-Chao Zhang 1 , Qian Wang 1 , Yan-Yan Li 1 , Ci Xu 1 , Yuan-Hua Liu 3 , Yuan Yao 4 , Dong Li 1 1 Department of Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 2 Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China 3 Department of Chemotherapy, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China 4 Department of Radiation Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China * These authors have contributed equally to this work Correspondence to: Dong Li, email: lidong@shsmu.edu.cn Keywords: metformin, pancreatic cancer, diabetes, overall survival Received: August 29, 2016      Accepted: January 24, 2017      Published: February 25, 2017 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.