title: No association between metformin use and survival in patients with pancreatic cancer: An observational cohort study.
abstract: Several studies have suggested an association between use of metformin and an increased overall survival in patients diagnosed with pancreatic cancer, however with several important methodological limitations. The aim of the study was to assess the association between overall survival, pancreatic cancer, and metformin use.A retrospective cohort study of 1111 patients with pancreatic cancer was conducted using data from The Netherlands Comprehensive Cancer Organization (1998-2011). Data were linked to the PHARMO Database Network containing drug-dispensing records from community pharmacies. Patients were classified as metformin user or sulfonylurea derivatives user from the moment of first dispensing until the end of follow up. The difference in overall survival between metformin users and nonusers was assessed, and additionally between metformin users and sulfonylurea derivatives users. Univariable and multivariable parametric survival models were used and use of metformin and sulfonylurea derivatives was included as time-varying covariates.Of the 1111 patients, 91 patients were excluded because of differences in morphology, 48 patients because of using merely metformin before diagnosis, and 57 metformin-users ever used contemporary sulfonylurea derivatives and were therefore excluded. Lastly, 8 patients with a survival of zero months were excluded. This resulted in 907 patients for the analysis. Overall, 77 users of metformin, 43 users of sulfonylurea derivatives, and 787 nonusers were identified. The adjusted rate ratio for overall survival for metformin users versus nonusers was 0.86 (95% CI: 0.66-1.11; P = 0.25). The difference in overall survival between metformin users and sulfonylurea derivatives users showed an adjusted rate ratio of 0.90 (95% CI: 0.59-1.40; P = 0.67).No association was found between overall survival, pancreatic cancer, and metformin use. This was in concordance with 2 recently published randomized controlled trials. Future research should focus on the use of adjuvant metformin in other cancer types and the development or repurposing of other drugs for pancreatic cancer.
authors.affiliation: Department of Surgical Oncology, Leiden University Medical Center, Leiden, The Netherlands, P.O. Box 9600, 2300 RC, The Netherlands Comprehensive Cancer Organisation The Netherlands, P.O. Box 231, 5600 AE, Eindhoven, The Netherlands PHARMO Institute for Drug Outcomes Research, van Deventerlaan 30/40, Utrecht, 3528 AE, The Netherlands.
authors.forename: Martine A
authors.initials: MA
authors.lastname: Frouws
authors.forename: Babs G
authors.initials: BG
authors.lastname: Sibinga Mulder
authors.forename: Esther
authors.initials: E
authors.lastname: Bastiaannet
authors.forename: Marjolein M J
authors.initials: MMJ
authors.lastname: Zanders
authors.forename: Myrthe P P
authors.initials: MPP
authors.lastname: van Herk-Sukel
authors.forename: Eleonora M
authors.initials: EM
authors.lastname: de Leede
authors.forename: Bert A
authors.initials: BA
authors.lastname: Bonsing
authors.forename: J Sven D
authors.initials: JSD
authors.lastname: Mieog
authors.forename: Cornelis J H
authors.initials: CJH
authors.lastname: Van de Velde
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Liefers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010190:Pancreatic Neoplasms / Q000150:complications / Q000401:mortality*; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin