title: The pharmacokinetic considerations and adverse effects of DPP-4 inhibitors [corrected].
abstract: BACKGROUND
  Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a class of anti-hyperglycemic agents with proven efficacy in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  This review considers the pharmacokinetic profile, adverse effects and drug interactions of DPP-4 inhibitors. DPP-4 inhibitors have certain differences in their structure, metabolism, route of elimination and selectivity for DPP-4 over structurally related enzymes, such as DPP-8/DPP-9. They have a low potential for drug interactions, with the exception of saxagliptin that is largely metabolized by cytochrome CYP3A4/A5. Reports of pancreatitis and pancreatic cancer have raised concerns regarding the safety of DPP-4 inhibitors and are under investigation. Post-marketing surveillance has revealed less common adverse effects, especially a number of skin- and immune-related adverse effects. These issues are covered in the present review.
  
  
  CONCLUSIONS
  DPP-4 inhibitors are useful and efficient drugs. DPP-4 inhibitors have similar mechanism of action and similar efficacy. However, DPP-4 inhibitors have certain differences in their pharmacokinetic properties that may be associated with different clinical effects and adverse event profiles. Although clinical trials indicated a favorable safety profile, post-marketing reports revealed certain safety aspects that need further investigation. Certainly, more research is needed to clarify if the differences among DPP-4 inhibitors could lead to a different clinical and safety profile.
authors.affiliation: Aristotle University of Thessaloniki, Hippokration Hospital, Medical School, Second Propedeutic Department of Internal Medicine , Thessaloniki , Greece.
authors.forename: Theodosios D
authors.initials: TD
authors.lastname: Filippatos
authors.forename: Vasilios G
authors.initials: VG
authors.lastname: Athyros
authors.forename: Moses S
authors.initials: MS
authors.lastname: Elisaf
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004151:Dipeptides / Q000009:adverse effects / Q000493:pharmacokinetics; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D000069476:Linagliptin; D009570:Nitriles / Q000009:adverse effects / Q000493:pharmacokinetics; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics; D010881:Piperidones / Q000009:adverse effects / Q000493:pharmacokinetics; D011687:Purines / Q000009:adverse effects / Q000493:pharmacokinetics; D011719:Pyrazines / Q000009:adverse effects / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000009:adverse effects / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000009:adverse effects / Q000493:pharmacokinetics; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics; D000068900:Sitagliptin Phosphate; D053778:Thiazolidines / Q000009:adverse effects / Q000493:pharmacokinetics; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000077597:Vildagliptin
chemical_list: C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; C534891:LC15-0444; D009570:Nitriles; D010880:Piperidines; D010881:Piperidones; D011687:Purines; D011719:Pyrazines; D011720:Pyrazoles; D011743:Pyrimidines; D011759:Pyrrolidines; D011799:Quinazolines; D053778:Thiazolidines; D014230:Triazoles; D000069476:Linagliptin; D014498:Uracil; C502994:saxagliptin; D000077597:Vildagliptin; C520853:alogliptin; C583175:anagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate
keywords: adverse effects; dipeptidyl-peptidase inhibitors; drug interactions; elimination; excretion; gliptins; metabolism; pharmacokinetics; safety; tolerability