title: DPP-4 inhibitors: pharmacological differences and their clinical implications.
abstract: BACKGROUND
  Recently, incretin-based therapy was introduced for the treatment of type 2 diabetes (T2D). In particular, dipeptidyl peptidase-4 inhibitors (DPP-4i) (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) play an increasing role in the management of T2D.
  
  
  METHODS
  An extensive literature search was performed to analyze the pharmacological characteristics of DPP-4i and their clinical implications.
  
  
  CONCLUSIONS
  DPP-4i present significant pharmacokinetic differences. They also differ in chemical structure, in the interaction with distinct subsites of the enzyme and in different levels of selectivity and potency of enzyme inhibition. Moreover, disparities in the effects on glycated hemoglobin, glucagon-like peptide-1 and glucagon levels and on glucose variability have been observed. However, indirect comparisons indicate that all DPP-4i have a similar safety and efficacy profiles. DPP-4i are preferred in overweight/obese and elderly patients because of the advantages of minimal or no influence on weight gain and low risk of hypoglycemia. For the same reasons, DPP-4i can be safely combined with insulin. However, currently cardiovascular outcomes related to DPP-4i are widely debated and the available evidence is controversial. Today, long-term studies are still in progress and upcoming results will allow us to better define the strengths and limits of this therapeutic class.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Department of Endocrinology , Barcelona , Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
authors.forename: Liberata
authors.initials: L
authors.lastname: Sportiello
authors.forename: Concetta
authors.initials: C
authors.lastname: Rafaniello
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D054795:Incretins / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin
keywords: dipeptidyl peptidase-4 inhibitors; glucose variability; pharmacodynamics; pharmacokinetics; pharmacology; type 2 diabetes