title: Are metformin, statin and aspirin use still associated with overall mortality among colorectal cancer patients with diabetes if adjusted for one another?
abstract: BACKGROUND
  Metformin, statin and aspirin use seem associated with decreased mortality in cancer patients, though, without adjusting for one another. Independent associations of these drugs with overall mortality after colorectal cancer (CRC) diagnosis within glucose-lowering drugs (GLDs) users were assessed.
  
  
  METHODS
  Patients starting GLDs before CRC diagnosis (1998-2011) were selected from the Eindhoven Cancer Registry linked with the PHARMO Database Network. The Cox regression model, with time since CRC diagnosis, included time-dependent variables of cumulative exposure to metformin, statins and aspirin after cancer diagnosis and time-dependent ever-never terms for drug exposure.
  
  
  RESULTS
  A total of 1043 patients used GLDs before CRC diagnosis; 666 (64%) used metformin, 639 (61%) used statins and 490 (47%) used aspirin after CRC diagnosis. Multivariable analyses revealed that longer cumulative exposure to metformin was not associated with overall mortality (HRCumulative exposure/6 months 1.02; 95% CI 0.97-1.07), whereas the favourable effect of statins increased with cumulative exposure (HRCumulative exposure/6 months 0.93; 95% CI 0.89-0.98). No association between aspirin use and overall mortality was seen (HRCumulative exposure/6 months 0.98; 95% CI 0.93-1.03).
  
  
  CONCLUSIONS
  No independent association between cumulative exposure to metformin, aspirin and overall mortality was found. Cumulative exposure to statins after CRC diagnosis was associated with lower overall mortality, supporting a drug effect of statins among GLDs users.
authors.affiliation: Department of Research, Netherlands Comprehensive Cancer Organisation, Eindhoven, The Netherlands.
authors.forename: M M J
authors.initials: MM
authors.lastname: Zanders
authors.affiliation: Department of Research, PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
authors.forename: M P P
authors.initials: MP
authors.lastname: van Herk-Sukel
authors.affiliation: 1] Department of Research, Netherlands Comprehensive Cancer Organisation, Eindhoven, The Netherlands [2] Department of Medical and Clinical Psychology, Centre of Research on Psychology in Somatic Diseases (CoRPS), Tilburg University, Tilburg, The Netherlands.
authors.forename: P A J
authors.initials: PA
authors.lastname: Vissers
authors.affiliation: Department of Research, PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
authors.forename: R M C
authors.initials: RM
authors.lastname: Herings
authors.affiliation: 1] Department of Internal Medicine, Máxima Medical Centre, Veldhoven, The Netherlands [2] Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands [3] Department of Health Services Research, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands.
authors.forename: H R
authors.initials: HR
authors.lastname: Haak
authors.affiliation: 1] Department of Research, Netherlands Comprehensive Cancer Organisation, Eindhoven, The Netherlands [2] Department of Medical and Clinical Psychology, Centre of Research on Psychology in Somatic Diseases (CoRPS), Tilburg University, Tilburg, The Netherlands.
authors.forename: L V
authors.initials: LV
authors.lastname: van de Poll-Franse
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D048909:Diabetes Complications / Q000453:epidemiology / Q000401:mortality; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D008687:Metformin; D001241:Aspirin