title: Impact of dipeptidyl peptidase-4 inhibitors on serum adiponectin: a meta-analysis.
abstract: BACKGROUND
  Adiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1). The present study aimed to evaluate the effect of DPP4i on serum adiponectin in T2DM patients.
  
  
  METHODS
  The PubMed, Embase, and Cochrane library databases were searched from inception to February 2016. Randomized controlled trials, evaluating the DPP4i (sitagliptin and vildagliptin) versus comparator (placebo or active-comparison), in T2DM patients with duration of ≥ 12 weeks, were identified. Weighted differences in means of adiponectin levels were calculated by using a fixed or random-effects model.
  
  
  RESULTS
  Ten randomized controlled trials, including 1,495 subjects, were identified. Compared with placebo, DPP4i (sitagliptin and vildagliptin) treatment significantly elevated adiponectin levels by 0.74 μg/mL (95% confidence interval [CI], 0.45 to 1.03) relative to that using an active-comparison by 0.00 μg/mL (95% CI, -0.57 to 0.56). Compared with active-comparison, vildagliptin treatment increased adiponectin levels by 0.32 μg/mL (95% CI, -0.01 to 0.65), whereas sitagliptin treatment decreased adiponectin levels by -0.24 μg/mL (95% CI, -1.07 to 0.58). Trials examining effects of other DPP4i were not found.
  
  
  CONCLUSIONS
  Sitagliptin and vildagliptin increased serum adiponectin levels and had no stronger effect than traditional oral antidiabetic drugs. Further trials with larger sample size are needed to confirm the results and investigate the association between serum adiponectin levels and treatment of other DPP-4 inhibitors.
  
  
  BACKGROUND
  Registration No in PROSPERO: CRD42016037399 .
authors.affiliation: Institute of Cardiovascular Sciences, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Men
authors.affiliation: Institute of Cardiovascular Sciences, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Suodi
authors.initials: S
authors.lastname: Zhai
authors.affiliation: Institute of Cardiovascular Sciences, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. georgeliu@bjmu.edu.cn.
authors.forename: George
authors.initials: G
authors.lastname: Liu
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D052242:Adiponectin / Q000097:blood*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068900:Sitagliptin Phosphate / Q000494:pharmacology / Q000627:therapeutic use; D000077597:Vildagliptin
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate
keywords: Adiponectin; Dipeptidyl peptidase-4 inhibitors; Sitagliptin; Type 2 diabetes mellitus; Vildagliptin