TY - JOUR
T1 - Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus
AU - Chen, Xiao Wu
AU - He, Zhi Xu
AU - Zhou, Zhi Wei
AU - Yang, Tianxin
AU - Zhang, Xueji
AU - Yang, Yin Xue
AU - Duan, Wei
AU - Zhou, Shu Feng
N1 - Publisher Copyright:
© 2015 Wiley Publishing Asia Pty Ltd.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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.
KW - Alogliptin
KW - Anagliptin
KW - Dipeptidyl peptidase-4 inhibitor
KW - Gemigliptin
KW - Linagliptin
KW - Saxagliptin
KW - Sitagliptin
KW - Teneligliptin
KW - Type 2 diabetes
KW - Vildagliptin
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U2 - 10.1111/1440-1681.12455
DO - 10.1111/1440-1681.12455
M3 - Article
C2 - 26173919
AN - SCOPUS:84941558262
SN - 0305-1870
VL - 42
SP - 999
EP - 1024
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
IS - 10
ER -