title: Conventional hypoglycaemic agents and the risk of lung cancer in patients with diabetes: a meta-analysis.
abstract: BACKGROUND
  Accumulating evidence suggests that hypoglycaemic agents influence lung cancer risk in patients with diabetes. It remains to be fully elucidated whether conventional hypoglycaemic agents (metformin, sulfonylureas, thiazolidinediones [TZDs] or insulin) affect lung cancer incidence in patients with diabetes.
  
  
  METHODS
  We performed a meta-analysis using EMBASE, MEDLINE and Web of Science to search randomised controlled trials (RCTs), cohort studies, and case-control studies published up to October 2013 that assessed the effects of metformin, sulfonylurea, TZDs or insulin on lung cancer risk in subjects with diabetes. Fixed and random effects meta-analysis models were used, and the effect size was expressed as a summary odds ratio (OR) with 95% confidence intervals (CI). The Grades of Research, Assessment, Development and Evaluation (GRADE) approach was applied to define the quality of the evidence.
  
  
  RESULTS
  Analysis of 15 studies (11 cohort studies, 2 case-control studies, and 2 RCTs) showed that metformin use was associated with a 15% reduction in risk of lung cancer (OR 0.85, 95% CI 0.77 to 0.92), but this finding was not supported by sub-analysis of smoking-adjusted studies (OR 0.84, 95% CI 0.61 to 1.06). Moreover, sulfonylurea or TZDs use was not associated with increased or decreased lung cancer risk, respectively (OR 1.10, 95% CI 0.93 to 1.26), (OR 0.86, 95% CI 0.70 to 1.02). Higher lung cancer risk was related to insulin (OR 1.23, 95% CI 1.10 to 1.35). However, all data from RCTs failed to demonstrate a statistically significant effect.
  
  
  CONCLUSIONS
  This analysis demonstrated that metformin use may reduce lung cancer risk in patients with diabetes but not in a smoking-adjusted subgroup and that insulin use may be associated with an increased lung cancer risk in subjects with diabetes.
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xue-Fei
authors.initials: XF
authors.lastname: Shi
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000150:complications*; D008687:Metformin / Q000627:therapeutic use; D017594:Publication Bias; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D008687:Metformin