title: Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus patients with moderate to severe renal impairment: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To perform a systematic review and meta-analysis regarding the efficacy and safety of dipeptidyl peptidase-4 (DDP-4) inhibitors ("gliptins") for the treatment of type 2 diabetes mellitus (T2DM) patients with moderate to severe renal impairment.
  
  
  METHODS
  All available randomized-controlled trials (RCTs) that assessed the efficacy and safety of DDP-4 inhibitors compared with placebo, no treatment, or active drugs were identified using PubMed, EMBASE, Cochrane CENTRAL, conference abstracts, clinical trials.gov, pharmaceutical company websites, the FDA, and the EMA (up to June 2014). Two independent reviewers extracted the data, and a random-effects model was applied to estimate summary effects.
  
  
  RESULTS
  Thirteen reports of ten studies with a total of 1,915 participants were included in the final analysis. Compared with placebo or no treatment, DPP-4 inhibitors reduced HbA1c significantly (-0.52%, 95%CI -0.64 to -0.39) and had no increased risk of hypoglycemia (RR 1.10, 95%CI 0.92 to 1.32) or weight gain. In contrast to glipizide monotherapy, DPP-4 inhibitors showed no difference in HbA1c lowering effect (-0.08%, 95% CI -0.40 to 0.25) but had a lower incidence of hypoglycemia (RR 0.40, 95%CI 0.23 to 0.69). Furthermore, DPP-4 inhibitors were well-tolerated, without any additional mortality and adverse events. However, the quality of evidence was mostly as low, as assessed using the GRADE system for each outcome.
  
  
  CONCLUSIONS
  DPP-4 inhibitors are effective at lowering HbA1c in T2DM patients with moderate to severe renal impairment. DPP-4 inhibitors also have a potential advantage in lowering the risk of adverse events. Regarding the low quality of the evidence according to GRADE, additional well-designed randomized trials that focus on the safety and efficacy of DPP-4 inhibitors in various CKD stages are needed urgently.
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fei
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
mesh_terms: D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D010919:Placebos; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000150:complications*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D010919:Placebos