Use of metformin was associated with a 16% reduced risk for overall mortality in patients with type 2 diabetes and pancreatic cancer.
In addition to treating patients with type 2 diabetes, recent research has shown that metformin expresses an anti-cancer effect through the rapamycin-signal pathway and the ataxia telangiectasia mutated/liver kinase B1/adenosine 5′-monophosphate-acted protein kinase axis. A relationship between cancer of the pancreas and type 2 diabetes exists, with a significantly higher incidence of cancer and cancer-related mortality in patients with diabetes. Previous epidemiologic research and meta-analysis have showcased the relationship between metformin use and pancreatic cancer risk; however, the relationship is still unclear.
This study utilized a meta-analysis of twenty-one studies, consisting of 38,722 patients. Studies were extracted from Pubmed, Embase, Ovid, and Cochrane. For this study, nineteen studies were cohorts, and two studies were randomized controlled studies (RCT). These studies’ observation period ranged from 1986 to 2015 and took place in Italy, Japan, Korea, New Zealand, Netherlands, or the USA. Studies included for analysis had to meet the inclusion criteria of being an RCT, observational, cohort, or case-controlled studies that showcased the relationship between the use of metformin and overall survival in patients diagnosed with pancreatic cancer concurrently with diabetes mellitus. Studies deemed eligible had to include patients treated with metformin before and after diagnosing pancreatic cancer. The study’s primary outcome is to assess metformin’s effect on patients’ survival outcome with pancreatic cancer with concurrent diabetes mellitus.
Multivariate Cox proportional hazard ratio (HR) was utilized for quantitative analysis. A pooled HR of > 1 suggested metformin use had an undesired prognosis, while a pooled HR < 1 indicated a favorable prognosis, for patients with pancreatic cancer. Statistically, significance was deemed if the 95% confidence interval (CI) of the HR did not overlap 1
Overall and subgroup populations were analyzed through study-specific HR and pooled HR. The use of metformin was associated with a 16% reduced risk for overall mortality compared to patients who did not receive metformin (HR = 0.83, 95% CI: 0.74-0.91, P<.001, I2=79.4). Patients from Asian and Western countries showed a significant benefit of metformin use in progression-free survival. However, when further analyzed amongst the different counties, a benefit of statistical significance was observed more in patients from Asian countries (HR = 0.77, 95% CI: 0.62-0.92, P< .001, I2 =79.9). Patients were also analyzed based on the cancer stage. Patients in the early and mixed stages of cancer had the highest survival benefit of metformin use (HR = 0.75, 95% CI: 0.64-0.85, P=.90 vs. HR = 0.81, 95% CI: 0.70-0.91, P<.001, respectively). However, patients with pancreatic cancer at advanced stages and receiving chemotherapy did not benefit from metformin use in survival benefit.
Through this study, the results indicated that a subset of patients with pancreatic cancer from Asian countries, including Korea and Japan, are more likely to see a benefit in using metformin for more prolonged survival. This meta-analysis also indicated that patients in the early and mixed stages of pancreatic cancer might experience the most significant survival benefit. This meta-analysis’s limitations included a limited representation from Asian countries; the studies analyzing Asian countries mainly comprised patients from Korea. Further studies should be conducted from neighboring Asian countries to assess the relationship between metformin use and survival rates in sub-specific Asian countries. Additional further studies on the initiation time of metformin, metformin dose, and duration of type 2 diabetes diagnosis, may also give more guidance on the relationship between survival rate and diabetes management.
- Properly managing diabetes may help improve the survival rate in patients with pancreatic cancer.
- Patients of Asian descent with pancreatic cancer and concurrent type 2 diabetes on metformin may experience a more significant survival benefit.
- Management of diabetes with metformin in patients in the early and mixed stages of pancreatic cancer may provide the most significant survival benefit.
Shi, Yu-Qi, et al. “Relationships Are between Metformin Use and Survival in Pancreatic Cancer Patients Concurrent with Diabetes.” Medicine
Tseng, Chin-Hsiao. “Metformin and Pancreatic Cancer Risk in Patients With Type 2 Diabetes.” Pancreas, vol. 47
Shana Indawala, PharmD Candidate, University of South Florida Health, Taneja College of Pharmacy