Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

Xiao Wu Chen, Zhi Xu He, Zhi Wei Zhou, Tianxin Yang, Xueji Zhang, Yin Xue Yang, Wei Duan, Shu Feng Zhou

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs that improve glycaemic control without causing weight gain or increasing hypoglycaemic risk in patients with type 2 diabetes mellitus (T2DM). The eight available DPP-4 inhibitors, including alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin, are small molecules used orally with identical mechanism of action and similar safety profiles in patients with T2DM. DPP-4 inhibitors may be used as monotherapy or in double or triple combination with other oral glucose-lowering agents such as metformin, thiazolidinediones, or sulfonylureas. Although DPP-4 inhibitors have the same mode of action, they differ by some important pharmacokinetic and pharmacodynamic properties that may be clinically relevant in some patients. The main differences between the eight gliptins include: potency, target selectivity, oral bioavailability, elimination half-life, binding to plasma proteins, metabolic pathways, formation of active metabolite(s), main excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug-drug interactions. The off-target inhibition of selective DPP-4 inhibitors is responsible for multiorgan toxicities such as immune dysfunction, impaired healing, and skin reactions. As a drug class, the DPP-4 inhibitors have become accepted in clinical practice due to their excellent tolerability profile, with a low risk of hypoglycaemia, a neutral effect on body weight, and once-daily dosing. It is unknown if DPP-4 inhibitors can prevent disease progression. More clinical studies are needed to validate the optimal regimens of DPP-4 inhibitors for the management of T2DM when their potential toxicities are closely monitored.

Original languageEnglish (US)
Pages (from-to)999-1024
Number of pages26
JournalClinical and Experimental Pharmacology and Physiology
Issue number10
StatePublished - Oct 1 2015
Externally publishedYes


  • Alogliptin
  • Anagliptin
  • Dipeptidyl peptidase-4 inhibitor
  • Gemigliptin
  • Linagliptin
  • Saxagliptin
  • Sitagliptin
  • Teneligliptin
  • Type 2 diabetes
  • Vildagliptin

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)


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