title: Clinical practice considerations and review of the literature for the Use of DPP-4 inhibitors in patients with type 2 diabetes and chronic kidney disease.
abstract: Many commonly prescribed agents for the treatment of type 2 diabetes (T2DM) have important restrictions on use in patients with renal impairment. Prescribing information and published data on dipeptidyl peptidase-4 (DPP-4) inhibitors indicate that these agents are suitable for use in this patient population. However, a recent database analysis indicated prevalent underrecognition of renal impairment and limited awareness of prescription considerations associated with DPP-4 inhibitor use in patients with renal impairment. Thus, this article reviews recent literature on the safety, efficacy, pharmacokinetics, and clinical use of DPP-4 inhibitors in patients with renal impairment and T2DM.
  
  
  
  PubMed searches were conducted for literature describing the use of DPP-4 inhibitors in patients with renal impairment.
  
  
  
  Most DPP-4 inhibitors are characterized by significant renal clearance. As a result, pharmacokinetics are measurably affected by the presence of renal impairment; plasma exposure of DPP-4 inhibitors and their metabolites may increase by up to sevenfold in severe impairment/end-stage renal disease. The exception in this case is linagliptin, which is eliminated predominantly via the hepatobiliary system. Our search identified several studies that evaluated specific doses of DPP-4 inhibitors in patients with renal impairment and reported positive safety and efficacy results.
  
  
  
  Overall, DPP-4 inhibitors are an effective means of controlling blood glucose in patients with T2DM and renal impairment. Considering the restrictions associated with many other antihyperglycemic agents when used in patients with renal impairment, DPP-4 inhibitors should be a considered as a treatment option in this patient population.
authors.affiliation: Tampa Bay Nephrology Associates, PL, Tampa, Florida.
authors.forename: German
authors.initials: G
authors.lastname: Ramirez
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Morrison
authors.forename: Polly A
authors.initials: PA
authors.lastname: Bittle
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004151:Dipeptides / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000069476:Linagliptin; D009570:Nitriles / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D011687:Purines / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D011719:Pyrazines / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D011759:Pyrrolidines / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D000077597:Vildagliptin
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D010880:Piperidines; D011687:Purines; D011719:Pyrazines; D011759:Pyrrolidines; D011799:Quinazolines; D014230:Triazoles; D000069476:Linagliptin; D014498:Uracil; C502994:saxagliptin; D000077597:Vildagliptin; C520853:alogliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate