Young Seok Seo, Hyung Jin Choi, Mi Sook Kim, Jin A. Choi, Won Il Jang, Shin Hee Kang, Eun Kyung Paik, Yeon Ju Kim, Hyung Jun Yoo, Sang Beom Kim, Yun Jung Kim, Ha Jin Tchoe, Jin-Kyu Kang, Hyo Jeong Kim, Min Jung Ko, Chan Mi Park, Chul Ju Han, and Ae Jung Jo more...
// Won Il Jang 1, * , Mi-Sook Kim 1, 2 , Shin Hee Kang 2, * , Ae Jung Jo 2 , Yun Jung Kim 2 , Ha Jin Tchoe 2 , Chan Mi Park 2 , Hyo Jeong Kim 2 , Jin A Choi 2 , Hyung Jin Choi 3 , Eun-Kyung Paik 1 , Young Seok Seo 1 , Hyung Jun Yoo 1 , Jin-Kyu Kang 1 , Chul Ju Han 4 , Yeon Ju Kim 4 , Sang Beom Kim 5 , Min Jung Ko 2 1 Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea 2 Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea 3 Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Republic of Korea 4 Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea 5 Department of Surgery, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea * These authors contributed equally to this work and share co-first author Correspondence to: Mi-Sook Kim, email: mskim@kirams.re.kr Min Jung Ko, email: minjungko@neca.re.kr Keywords: pancreatic cancer, resection, diabetes, metformin, nationwide database Received: October 04, 2016 Accepted: November 24, 2016 Published: January 05, 2017 ABSTRACT Background: Preclinical 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. Results: A 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 Methods: Data 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. Conclusions: This 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. more...