title: Tolerability of dipeptidyl peptidase-4 inhibitors: a review.
abstract: BACKGROUND
  Oral glucose-lowering agents are used to treat patients with type 2 diabetes mellitus (T2DM). Most patients require multiple agents to maintain glycemic targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors are administered as monotherapy and in combination therapy for the treatment of T2DM.
  
  
  OBJECTIVE
  The aim of this article was to provide a thorough review of published tolerability data on 5 DPP-4 inhibitors.
  
  
  METHODS
  PubMed and Web of Science were searched for English-language clinical trials published from January 2000 to June 2001, using the following key words: dipeptidyl peptidase-4 inhibitor, vildagliptin, alogliptin, sitagliptin, saxagliptin, linagliptin, safety, tolerability, efficacy, effect, AE, and adverse effect. Studies were considered for inclusion if they were randomized, double-blind trials performed in patients ≥18 years of age with T2DM and with a hemoglobin A(1c) of ≥6.5%; included ≥1 arm that received monotherapy with DPP-4; and reported adverse events (AEs). Studies in patients with a history of type 1 or secondary forms of diabetes, significant diabetic complications or cardiovascular disease within the 6 months before the start of the study, hepatic disease or abnormalities, and/or renal abnormalities were excluded.
  
  
  RESULTS
  A total of 45 clinical trials, 5 pharmacokinetic studies, and 28 meta-analyses or reviews were included. The duration of studies ranged from 7 days to 104 weeks. The most commonly reported AEs were nasopharyngitis, upper respiratory infections, all-cause infections, headache, gastrointestinal symptoms, and musculoskeletal pain. Based on the findings from the studies, the DPP-4 inhibitors had minimal impact on weight and were not associated with an increased risk for hypoglycemia relative to placebo. Rates of nasopharyngitis were higher with the DDP-4 inhibitors than with placebo. Pancreatitis was reported at lower rates with the DPP-4 inhibitors compared with other oral antihyperglycemic agents. Cardiovascular events were limited, and postmarketing studies are ongoing.
  
  
  CONCLUSIONS
  The tolerability of DPP-4 inhibitors is supported by published clinical trials. The rates of weight gain, gastrointestinal AEs, and hypoglycemia were minimal with the DPP-4 inhibitors studied.
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Richard
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Shelburne
authors.forename: Julienne K
authors.initials: JK
authors.lastname: Kirk
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D010919:Placebos; D016032:Randomized Controlled Trials as Topic
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D010919:Placebos