S Amin1, G Mhango2, J Lin2, A Aronson1, J Wisnivesky2, P Boffetta3, Aimee L Lucas1. 1. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 2. Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 3. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Abstract
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. Diabetes mellitus (DM) is both a risk factor for and a sequela of PDAC. Metformin is a commonly prescribed biguanide oral hypoglycemic used for the treatment of type II DM. We investigated whether metformin use before PDAC diagnosis affected survival of patients with DM, controlling confounders such as diabetic severity. METHODS: We used the Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database to identify patients with PDAC diagnosed between 2007 and 2011. The diabetic TO comorbidity severity index (DCSI) controlled for DM severity. Inverse propensity weighted Cox Proportional-Hazard Models assessed the association between metformin use and overall survival adjusting for relevant confounders. RESULTS: We identified 1,916 patients with PDAC and pre-existing DM on hypoglycemic medications at least 1 year before cancer diagnosis. Of these, 1,098 (57.3%) were treated with metformin and 818 (42.7%) with other DM medications. Mean survival for those on metformin was 5.5 months compared with 4.2 months for those not on metformin (P<0.01). After adjusting for confounders including DCSI, Charlson score, and chronic kidney disease (CKD), patients on metformin had a 12% decreased risk of mortality compared with patients on other medications (hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.81-0.96, P<0.01). In stratified analysis, differences persisted regardless of the Charlson score, the DCSI score, the presence of kidney disease, or the use of insulin/other hypoglycemic medications (P<0.01 for all). CONCLUSIONS: Metformin is associated with increased survival among diabetics with PDAC. If confirmed in a prospective study, then these results suggest a possible role for metformin as an adjunct to chemotherapy among diabetics with PDAC.
OBJECTIVES:Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. Diabetes mellitus (DM) is both a risk factor for and a sequela of PDAC. Metformin is a commonly prescribed biguanide oral hypoglycemic used for the treatment of type II DM. We investigated whether metformin use before PDAC diagnosis affected survival of patients with DM, controlling confounders such as diabetic severity. METHODS: We used the Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database to identify patients with PDAC diagnosed between 2007 and 2011. The diabetic TO comorbidity severity index (DCSI) controlled for DM severity. Inverse propensity weighted Cox Proportional-Hazard Models assessed the association between metformin use and overall survival adjusting for relevant confounders. RESULTS: We identified 1,916 patients with PDAC and pre-existing DM on hypoglycemic medications at least 1 year before cancer diagnosis. Of these, 1,098 (57.3%) were treated with metformin and 818 (42.7%) with other DM medications. Mean survival for those on metformin was 5.5 months compared with 4.2 months for those not on metformin (P<0.01). After adjusting for confounders including DCSI, Charlson score, and chronic kidney disease (CKD), patients on metformin had a 12% decreased risk of mortality compared with patients on other medications (hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.81-0.96, P<0.01). In stratified analysis, differences persisted regardless of the Charlson score, the DCSI score, the presence of kidney disease, or the use of insulin/other hypoglycemic medications (P<0.01 for all). CONCLUSIONS:Metformin is associated with increased survival among diabetics with PDAC. If confirmed in a prospective study, then these results suggest a possible role for metformin as an adjunct to chemotherapy among diabetics with PDAC.
Authors: Jenny J Lin; Emily J Gallagher; Keith Sigel; Grace Mhango; Matthew D Galsky; Cardinale B Smith; Derek LeRoith; Juan P Wisnivesky Journal: Am J Respir Crit Care Med Date: 2015-02-15 Impact factor: 21.405
Authors: H O Adami; W H Chow; O Nyrén; C Berne; M S Linet; A Ekbom; A Wolk; J K McLaughlin; J F Fraumeni Journal: J Natl Cancer Inst Date: 1996-10-16 Impact factor: 13.506
Authors: Craig J Currie; Chris D Poole; Sara Jenkins-Jones; Edwin A M Gale; Jeffrey A Johnson; Christopher Ll Morgan Journal: Diabetes Care Date: 2012-01-20 Impact factor: 19.112
Authors: Roger C Zhu; Kirk Rattanakorn; Steven Pham; Divya Mallam; Thomas McIntyre; Moro O Salifu; Irini Youssef; Samy I McFarlane; Shivakumar Vignesh Journal: Colorectal Cancer Date: 2017-06-21
Authors: Guido Eibl; Zobeida Cruz-Monserrate; Murray Korc; Maxim S Petrov; Mark O Goodarzi; William E Fisher; Aida Habtezion; Aurelia Lugea; Stephen J Pandol; Phil A Hart; Dana K Andersen Journal: J Acad Nutr Diet Date: 2017-09-12 Impact factor: 4.910
Authors: Hao Liu; Kamila Naxerova; Matthias Pinter; Joao Incio; Hang Lee; Kohei Shigeta; William W Ho; Jonathan A Crain; Alex Jacobson; Theodoros Michelakos; Daniella Dias-Santos; Andrea Zanconato; Theodore S Hong; Jeffrey W Clark; Janet E Murphy; David P Ryan; Vikram Deshpande; Keith D Lillemoe; Carlos Fernandez-Del Castillo; Michael Downes; Ronald M Evans; James Michaelson; Cristina R Ferrone; Yves Boucher; Rakesh K Jain Journal: Clin Cancer Res Date: 2017-06-09 Impact factor: 12.531
Authors: Adetunji T Toriola; Suhong Luo; Theodore S Thomas; Bettina F Drake; Su-Hsin Chang; Kristen M Sanfilippo; Kenneth R Carson Journal: Cancer Epidemiol Biomarkers Prev Date: 2019-11-04 Impact factor: 4.090