title: Factors Related to the Glucose-Lowering Efficacy of Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Meta-Analysis Focusing on Ethnicity and Study Regions.
abstract: OBJECTIVE
  Several systematic reviews and meta-analyses have been conducted including an analysis to investigate the difference between ethnic groups in the glucose-lowering efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors. This study assessed the factors related to the glucose-lowering efficacy and explored potential differences among ethnicities; in particular, Japanese subjects were dealt separately from other Asian subjects.
  
  
  METHODS
  A systematic literature search was conducted using the MEDLINE, EMBASE, Cochrane Central Register, Japan Medical Abstracts Society, and ClinicalTrials.gov databases. Electronically searchable study results from the US/EU/Japanese regulatory approval reviews were also used. The weighted mean difference (WMD) for glycosylated hemoglobin (HbA1c) change from baseline in DPP-4 inhibitors compared with placebo was calculated. Heterogeneity was assessed by using the Q statistic and I2statistic. Univariate and multivariate meta-regression analyses were performed.
  
  
  RESULTS
  The literature search identified 79 studies with 91 arms and 25,095 patients. The WMD in the change from baseline of HbA1cbetween the DPP-4 inhibitor group and placebo group was -0.695% (95% confidence interval -0.734 to -0.656) with considerable heterogeneity (I2= 69.7%). In univariate meta-regression, factors including study duration, percentage of males, age, duration of diabetes mellitus, baseline HbA1cvalues, body mass index, body weight, and percentage of Asian subjects showed associations with the glucose-lowering efficacy. Additionally, studies in Asian subjects, studies in Japanese subjects, and studies conducted in Japan showed relations when three classifications regarding ethnicity and study regions were applied. In multivariate meta-regression, studies in Japanese subjects/studies conducted in Japan as well as the baseline HbA1cvalues were identified as influencing factors.
  
  
  CONCLUSIONS
  These identified factors-Japanese subjects/studies conducted in Japan and the baseline HbA1cvalues-should be taken into account when planning and conducting future clinical studies.
authors.affiliation: Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. kayo.fujita@pfizer.com.
authors.forename: Kayo
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Narukawa
mesh_terms: D044466:Asian People; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D005006:Ethnicity; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007564:Japan; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents