title: Metformin Use Is Associated with Improved Survival in Patients Undergoing Resection for Pancreatic Cancer.
abstract: Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD = 9.1 years). Roughly one half of patients were female (n = 1735, 51.1 %); 49.1 % (n = 1665) presented with a Charlson comorbidity index of 3 or greater (CCI ≥3); and 19.6 % (n = 664) had diabetes. At the time of surgery, 60.0 % (n = 2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n = 1212) a partial/distal pancreatectomy, while 4.3 % (n = 147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p = 0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4-67.3 %] vs. 69.2 % [95 % CI 64.2-73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR] = 0.79, 95 % CI 0.67-0.93, p = 0.005). Metformin use was associated with an improved overall survival among patients undergoing pancreatic surgery for pancreatic cancer. Further work is necessary to better understand its role in modifying cancer-specific and overall health outcomes.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cerullo
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA.
authors.forename: Faiz
authors.initials: F
authors.lastname: Gani
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA.
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Canner
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA. tpawlik1@jhmi.edu.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D003920:Diabetes Mellitus / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000601:surgery*; D016577:Pancreaticoduodenectomy; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Metformin; Pancreatic cancer; Survival post-surgery