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

Chen, Xiao-Wu, He, Zhi-Xu, Zhou, Zhi-Wei, Yang, Tianxin, Zhang, Xueji, Yang, Yin-Xue, Duan, Wei and Zhou, Shu-Feng 2015, Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus, Clinical and experimental pharmacology and physiology, vol. 42, no. 10, pp. 999-1024.

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Title Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus
Author(s) Chen, Xiao-Wu
He, Zhi-Xu
Zhou, Zhi-Wei
Yang, Tianxin
Zhang, Xueji
Yang, Yin-Xue
Duan, Wei
Zhou, Shu-Feng
Journal name Clinical and experimental pharmacology and physiology
Volume number 42
Issue number 10
Start page 999
End page 1024
Total pages 26
Publisher Wiley
Place of publication London, Eng.
Publication date 2015-10
ISSN 1440-1681
Keyword(s) alogliptin
anagliptin
dipeptidyl peptidase-4 inhibitor
gemigliptin
linagliptin
saxagliptin
sitagliptin
teneligliptin
type 2 diabetes
vildagliptin
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Physiology
INCRETIN-BASED THERAPIES
GLUCAGON-LIKE PEPTIDE-1
SEVERE RENAL IMPAIRMENT
PLACEBO-CONTROLLED TRIAL
LONG-TERM EXTENSION
DRUG-NAIVE PATIENTS
BETA-CELL FUNCTION
ADD-ON THERAPY
STEADY-STATE PHARMACOKINETICS
INITIAL COMBINATION THERAPY
Summary 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.
Language eng
Field of Research 0606 Physiology
1115 Pharmacology And Pharmaceutical Sciences
1116 Medical Physiology
111502 Clinical Pharmacology and Therapeutics
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Wiley
Persistent URL http://hdl.handle.net/10536/DRO/DU:30080716

Document type: Journal Article
Collection: School of Medicine
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