title: Systematic Literature Review of DPP-4 Inhibitors in Patients with Type 2 Diabetes Mellitus and Renal Impairment.
abstract: BACKGROUND
  Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the management of patients with type 2 diabetes mellitus (T2DM) and renal impairment (RI). A systematic literature review was performed to compare the efficacy and safety of DPP-4 inhibitors in patients with T2DM and RI.
  
  
  METHODS
  We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials (cut-off, June 2015) to identify ≥12-week, randomized, placebo-controlled trials on DPP-4 inhibitors in ≥50 patients with T2DM and RI. Outcomes of interest included change in glycated hemoglobin (HbA1c), overall safety, and incidence of hypoglycemic events (HEs).
  
  
  RESULTS
  Seven trials of ≤52-54 weeks duration were retrieved, which included one study each on vildagliptin, saxagliptin, and sitagliptin, two on linagliptin, and the remaining two were extension studies of vildagliptin and saxagliptin. Majority of patients were on insulin at baseline (53-86%), except in the sitagliptin study, where approximately 11% received insulin during the placebo-controlled phase. After 52 weeks, vildagliptin and saxagliptin reduced HbA1c levels by 0.6-0.7% (baseline 7.8-8.4%) versus placebo in the overall population. HbA1c reductions were similar at weeks 12 and 52. In the 12-week, placebo-controlled phase, sitagliptin and linagliptin reduced mean HbA1c by approximately 0.4% (baseline 7.7-8.1%) versus placebo. Rates of HEs with DPP-4 inhibitors were not significantly different versus placebo in any study. Rates of adverse events (AEs) and changes involving renal function were similar in the active- and placebo-treated groups.
  
  
  CONCLUSIONS
  These results suggest that DPP-4 inhibitors have the potential to improve glycemic control in patients with RI without increasing the risk of HEs or overall AEs.
  
  
  BACKGROUND
  Novartis Pharma AG.
authors: Baker IDI Heart and Diabetes Institute, Melbourne, Australia. merlin.thomas@bakeridi.edu.au.
authors: Merlin C
authors: http://orcid.org/0000-0002-2478-3586
authors: MC
authors: Thomas
authors: Novartis Pharma AG, Basel, Switzerland.
authors: Päivi M
authors: PM
authors: Paldánius
authors: Analysis Group Inc., Boston, MA, USA.
authors: Rajeev
authors: R
authors: Ayyagari
authors: Novartis Pharma AG, Basel, Switzerland.|Vifor Pharma Ltd., Glattbrugg, Switzerland.
authors: Siew Hwa
authors: SH
authors: Ong
authors: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.|Abdominal Centre Helsinki, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Folkhälsan Institute of Genetics, Folkhälsan Research Centre, Biomedicum Helsinki, Helsinki, Finland.
authors: Per-Henrik
authors: PH
authors: Groop
keywords: DPP-4 inhibitors; Linagliptin; Saxagliptin; Sitagliptin; Type 2 diabetes mellitus; Vildagliptin