title: Metformin and sulfonylureas in relation to cancer risk in type II diabetes patients: a meta-analysis using primary data of published studies.
abstract: BACKGROUND
  Accumulating evidence suggests that patients with type 2 diabetes mellitus (T2DM) and hyperinsulinemia are at increased risk for developing malignancies. It remains to be fully elucidated whether use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affect cancer incidence in subjects with T2DM.
  
  
  METHODS
  We performed a meta-analysis using PubMed, of randomized control trials (RCTs), cohorts, and case-control studies published through July 2012 that assess effects of metformin and/or sulfonylurea sulfonylureas on cancer risk at any site, in subjects with T2DM. Fixed and random effects meta-analysis models were used, and the effect size was summarized as relative risk (RR) for RCTs/cohorts and as odds ratio (OR) for the case-control studies.
  
  
  RESULTS
  Analysis of 24 metformin studies in subjects with T2DM showed that metformin use is associated with reduced risk for the development of cancer, in both cohort (RR=0.70 [95% CI=0.67-0.73]) and case-control studies (OR=0.90 [95% CI=0.84-0.98]), but this finding was not supported by RCTs (RR=1.01[95% CI=0.81-1.26]). Data from 18 sulfonylurea studies in subjects with T2DM showed that sulfonylurea use is associated with an increase in all-cancer risk, in cohort studies (RR=1.55 [95% CI=1.48 -1.63]), though data from RCTs (RR=1.17 [95% CI=0.95-1.45]) and case-control studies (OR=1.02 [95% CI=0.93-1.13]) failed to demonstrate a statistically significant effect.
  
  
  CONCLUSIONS
  This analysis using pooled primary data demonstrates that metformin use reduces, while sulfonylurea use may be associated with an increased cancer risk in subjects with T2DM. These findings need to be confirmed in large-scale RCTs before they are translated into clinical practice.
authors: Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA. Bindiya.Thakkar@bmc.org
authors: Bindiya
authors: B
authors: Thakkar
authors: Konstantinos N
authors: KN
authors: Aronis
authors: Maria T
authors: MT
authors: Vamvini
authors: Kelsey
authors: K
authors: Shields
authors: Christos S
authors: CS
authors: Mantzoros
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D019317:Evidence-Based Medicine; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D009369:Neoplasms / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D012306:Risk; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin