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.