title: Impact of three oral antidiabetic drugs on markers of β-cell function in patients with type 2 diabetes: a meta-analysis.
abstract: BACKGROUND
  The effect of metformin, pioglitazone and sitagliptin on β-cell function in the treatment of type 2 diabetes is controversial. Therefore, we performed a systematic review and meta-analysis to obtain a better understanding in the β-cell effects of metformin, pioglitazone and sitagliptin.
  
  
  METHODS
  We searched Pubmed and the Cochrane Center Register of Controlled Trials to identify relevant studies. Trials investigating effects of sitagliptin, metformin or pioglitazone on β-cell function were identified. The primary outcomes were homeostasis model assessment of β-cells (HOMA-β) and proinsulin/insulin ratio (PI/IR). Secondary outcome was hemoglobin A1c level. We used version 2 of the Comprehensive Meta Analysis software for all statistical analyses.
  
  
  RESULTS
  Metformin monotherapy was more effective than sitagliptin in improving HOMA-β (18.01% (95% CI 11.09% to 24.94%) vs. 11.29% (95% CI 9.21% to 13.37%), P = 0.040) and more effective (-0.137 (95% CI -0.082 to -0.192)) than both sitagliptin (-0.064 (95% CI -0.036 to -0.092), P = 0.019) and pioglitazone (-0.068 (95% CI -0.044 to -0.093), P = 0.015) in decreasing PI/IR. Metformin and sitagliptin combined (40.23% (95%CI 32.30% to 48.16%)) were more effective than sitagliptin and pioglitazone (11.82% (95% CI 6.61% to 17.04%), P = 0.000) and pioglitazone and metformin(9.81% (95% CI 1.67% to 17.95%), P = 0.022) in improving HOMA-β and decreasing PI/IR (-0.177 (95% CI -0.118 to -0.237); -0.080 (95% CI -0.045 to -0.114), P = 0.007; -0.038 (95% CI, -0.005 to 0.071), P = 0.023).
  
  
  CONCLUSIONS
  The included RCTs were of short duration (12-54 weeks). We could not determine long term effects on β-cells.
  
  
  CONCLUSIONS
  Metformin improves β-cell function more effectively than pioglitazone or sitagliptin in type 2 diabetes patients. Metformin and sitagliptin improved HOMA-β and PI/IR more than other combinations.
authors.affiliation: Department of Endocrinology, Changhai hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Lu
authors.forename: Jiajie
authors.initials: J
authors.lastname: Zang
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D000077205:Pioglitazone; D011384:Proinsulin / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D000077205:Pioglitazone; D011384:Proinsulin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones; D014230:Triazoles