Abstract
BackgroundPreclinical studies support an antitumor effect of metformin. However, clinical studies have conflicting results and metformin's effect remains controversial. The aim of this study was to evaluate metformin's effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection.ResultsA total of 764 patients underwent curative resection, met none of the exclusion criteria, and were prescribed oral hypoglycemic agents. The cancer-specific survival (5-year, 31.9% vs. 22.2%, p < 0.001) was significantly higher in the 530 metformin users than in the 234 diabetic metformin non-users. After multivariable adjustments, metformin users had significantly lower cancer-specific mortality as compared with metformin non-users (hazard ratio, 0.727; 95% confidence interval, 0.611–0.868). Cubic spline regression analysis demonstrated significantly decreased cancer-specific mortality with increasing dose of metformin (p = 0.0047).Materials and MethodsData were provided from the Korea Central Cancer Registry and the National Health Insurance Service in the Republic of Korea. The study cohort consisted of 28,862 patients newly diagnosed with pancreatic cancer between 2005 and 2011. Metformin exposure was determined from prescription information from 6 months before the first diagnosis of pancreatic cancer to last follow-up. The main outcome was cancer-specific survival.ConclusionsThis large study indicates that metformin might decrease cancer-specific mortality rates in localized resectable pancreatic cancer patients with pre-existing diabetes, independently of other factors, with a dose-response relationship.
Highlights
Pancreatic cancer has become the seventh leading cause of cancer mortality in the world
There were no significant difference between the metformin user group and non-user group in terms of age, sex, alcohol drinking behavior, regular exercise, body mass index (BMI), total cholesterol, fasting blood glucose, gamma-glutamyl transpeptidase, Charlson comorbidity index, treatment methods such as radiotherapy, chemotherapy, or types of surgery (Table 1)
In the metformin user group, the adjusted risk for cancer-specific mortality was significantly lower for patients with an medication possession ratio (MPR) ≥ 80% compared to those with an MPR < 80% (HR, 0.595; 95% confidence interval (CI), 0.468–0.757) (Table 2)
Summary
Pancreatic cancer has become the seventh leading cause of cancer mortality in the world. The prognosis for patients with pancreatic cancer remains extremely dismal, with a 5-year relative survival rate of only 7% [2]. Diabetes appears to be a risk factor for the development of pancreatic cancer [6]. Diabetes may affect treatment outcomes of patients with pancreatic cancer, the evidence is not consistent [7,8,9]. Anti-diabetic medications have been reported to affect pancreatic cancer risk. Metformin usage has been found to be associated with a reduced risk of pancreatic cancer [11]. The aim of this study was to evaluate metformin’s effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection
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