DPP-4 inhibitors: Pharmacological differences and their clinical implications

Antonio Ceriello, Liberata Sportiello, Concetta Rafaniello, Francesco Rossi

Research output: Contribution to journalArticlepeer-review


Introduction: 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.Areas covered: An extensive literature search was performed to analyze the pharmacological characteristics of DPP-4i and their clinical implications.Expert opinion: 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.

Original languageEnglish
JournalExpert Opinion on Drug Safety
Issue numberSUPPL. 1
Publication statusPublished - 2014


  • Dipeptidyl peptidase-4 inhibitors
  • Glucose variability
  • Pharmacodynamics
  • Pharmacokinetics
  • Pharmacology
  • Type 2 diabetes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Medicine(all)


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