title: Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: Department of General Surgery, The First People's Hospital of Shunde, Southern Medical University, Shunde, Foshan, Guangdong, China.
authors.forename: Xiao-Wu
authors.initials: XW
authors.lastname: Chen
authors.affiliation: Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Centre & Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, Guizhou, China.
authors.forename: Zhi-Xu
authors.initials: ZX
authors.lastname: He
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhou
authors.affiliation: Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Centre, Salt Lake City, UT, USA.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
authors.affiliation: Research Centre for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, China.
authors.forename: Xueji
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Yin-Xue
authors.initials: YX
authors.lastname: Yang
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Vic., Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
authors.affiliation: Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Centre & Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, Guizhou, China.|Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D012449:Safety
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors
keywords: alogliptin; anagliptin; dipeptidyl peptidase-4 inhibitor; gemigliptin; linagliptin; saxagliptin; sitagliptin; teneligliptin; type 2 diabetes; vildagliptin