Do we know the true mechanism of action of the DPP-4 inhibitors?

TY - JOUR

T1 - Do we know the true mechanism of action of the DPP-4 inhibitors?

AU - Andersen, Emilie S.

AU - Deacon, Carolyn F.

AU - Holst, Jens Juul

PY - 2018

Y1 - 2018

N2 - The prevalence of type 2 diabetes is increasing, which is alarming because of its serious complications. Anti-diabetic treatment aims to control glucose homeostasis as tightly as possible in order to reduce these complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a recent addition to the anti-diabetic treatment modalities, and have become widely accepted because of their good efficacy, their benign side-effect profile and their low hypoglycaemia risk. The actions of DPP-4 inhibitors are not direct, but rather are mediated indirectly through preservation of the substrates they protect from degradation. The two incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, are known substrates, but other incretin-independent mechanisms may also be involved. It seems likely therefore that the mechanisms of action of DPP-4 inhibitors are more complex than originally thought, and may involve several substrates and encompass local paracrine, systemic endocrine and neural pathways, which are discussed here.

AB - The prevalence of type 2 diabetes is increasing, which is alarming because of its serious complications. Anti-diabetic treatment aims to control glucose homeostasis as tightly as possible in order to reduce these complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a recent addition to the anti-diabetic treatment modalities, and have become widely accepted because of their good efficacy, their benign side-effect profile and their low hypoglycaemia risk. The actions of DPP-4 inhibitors are not direct, but rather are mediated indirectly through preservation of the substrates they protect from degradation. The two incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, are known substrates, but other incretin-independent mechanisms may also be involved. It seems likely therefore that the mechanisms of action of DPP-4 inhibitors are more complex than originally thought, and may involve several substrates and encompass local paracrine, systemic endocrine and neural pathways, which are discussed here.

KW - dipeptidyl peptidase-4 inhibitors

KW - incretin therapy

KW - type 2 diabetes

U2 - 10.1111/dom.13018

DO - 10.1111/dom.13018

M3 - Journal article

C2 - 28544214

SN - 1462-8902

VL - 20

SP - 34

EP - 41

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 1

ER -