Association between metformin use and mortality in patients with type 2 diabetes mellitus and localized resectable pancreatic cancer: a nationwide population-based study in korea
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Won Il Jang1,*, Mi-Sook Kim1,2, Shin Hee Kang2,*, Ae Jung Jo2, Yun Jung Kim2, Ha Jin Tchoe2, Chan Mi Park2, Hyo Jeong Kim2, Jin A Choi2, Hyung Jin Choi3, Eun-Kyung Paik1, Young Seok Seo1, Hyung Jun Yoo1, Jin-Kyu Kang1, Chul Ju Han4, Yeon Ju Kim4, Sang Beom Kim5, Min Jung Ko2
1Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
2Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea
3Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
4Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
5Department 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
Mi-Sook Kim, email: firstname.lastname@example.org
Min Jung Ko, email: email@example.com
Keywords: pancreatic cancer, resection, diabetes, metformin, nationwide database
Received: October 04, 2016 Accepted: November 24, 2016 Published: January 05, 2017
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.
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