title: Are sulfonylurea and insulin therapies associated with a larger risk of cancer than metformin therapy? A retrospective database analysis.
abstract: OBJECTIVE
  Several meta-analyses of observational studies suggested that metformin use reduces cancer risk in type 2 diabetes. However, this result was not confirmed by the few available randomized controlled trials (RCTs), and many observational studies on metformin and cancer were potentially afflicted with time-related bias. We aimed to avoid this bias when comparing cancer incidence in users of sulfonylurea, insulin, and other diabetes medications, respectively, with cancer incidence in metformin users.
  
  
  METHODS
  In a retrospective observational study, we used the German Disease Analyzer database with patient data from general practices throughout Germany. The study sample included 22,556 patients diagnosed with type 2 diabetes. During the median follow-up time of 4.8 years, 1,446 (6.4%) patients developed any cancer. In Cox regression analyses with either monotherapies or first diabetes medications as drug exposure, users of sulfonylurea (or insulin or other antidiabetes medications) were compared with metformin users.
  
  
  RESULTS
  In multivariable adjusted models, hazard ratios were 1.09 (95% CI 0.87-1.36) for sulfonylurea monotherapy, 1.14 (95% CI 0.85-1.55) for insulin monotherapy, and 0.94 (95% CI 0.67-1.33) for other diabetes medications compared with metformin monotherapy. Results were similar for comparison of first diabetes medications.
  
  
  CONCLUSIONS
  In a retrospective database analysis, taking into account potential time-related biases, no reduced cancer risk was found in metformin users. To clarify the association between diabetes medication and cancer risk, further well-designed observational studies and RCTs are needed.
authors.affiliation: German Diabetes Center, Institute for Biometrics and Epidemiology, Düsseldorf, Germany bernd.kowall@ddz.uni-duesseldorf.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kowall
authors.affiliation: German Diabetes Center, Institute for Biometrics and Epidemiology, Düsseldorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.affiliation: IMS Health, Frankfurt am Main, Germany.
authors.forename: Karel
authors.initials: K
authors.lastname: Kostev
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin