title: Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients.
abstract: OBJECTIVE
  The aim of this study was to look at the influence of metformin intake and duration, on urinary bladder cancer (UBC) risk, with sulfonylurea (SU) only users as control using a new user design (inception cohort).
  
  
  METHODS
  We conducted a retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) including all patients with at least one prescription of oral anti-diabetic drugs (ADD) and/or insulin. The risk of UBC in different groups of ADD users (metformin alone (one), metformin in combination (two) with other ADD medication (glinides, glitazones, DPP-4-inhibitors, SUs, insulin or more than one combination), all metformin users (1 + 2) was compared with SU only users using Cox proportional hazards models. The estimates were adjusted for age, gender, smoking status, BMI and diabetes duration.
  
  
  RESULTS
  The inception cohort included 165,398 participants of whom 132,960 were metformin users and 32,438 were SU only users. During a mean follow-up time of more than 5 years 693 patients developed UBC, 124 of the control group and 461 of the all metformin users. There was no association between metformin use and UBC risk (HR = 1.12, 95% CI 0.90, 1.40) compared with SU only users, even after adjustment for diabetes duration (HR = 1.13, 95% CI 0.90, 1.40). We found a pattern of decreasing risk of UBC with increasing duration of metformin intake, which was statistically not significant.
  
  
  CONCLUSIONS
  Metformin has no influence on the risk of UBC compared with SU in type 2 diabetes patients using a new user design.
authors.affiliation: Department of General Practice, KU Leuven, Leuven, Belgium.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Goossens
authors.affiliation: Department of General Practice, KU Leuven, Leuven, Belgium.|Department of General Practice, University of Maastricht, Maastricht.
authors.forename: Frank
authors.initials: F
authors.lastname: Buntinx
authors.affiliation: NUTRIM School of Nutrition, Metabolism and Toxicology, University of Maastricht, Maastricht.
authors.forename: Maurice P
authors.initials: MP
authors.lastname: Zeegers
authors.affiliation: Utrecht Institute of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht.|Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht.|Research Institute CAPHRI, University of Maastricht, the Netherlands.
authors.forename: J H M
authors.initials: JH
authors.lastname: Driessen
authors.affiliation: Utrecht Institute of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht.
authors.forename: Marie L
authors.initials: ML
authors.lastname: De Bruin
authors.affiliation: Utrecht Institute of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht.|Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht.|Research Institute CAPHRI, University of Maastricht, the Netherlands.|MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: De Vries
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000009:adverse effects*; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: bladder cancer; metformin; type 2 diabetes mellitus