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Diabetes Obes Metab. 2018 Jan;20(1):34-41. doi: 10.1111/dom.13018. Epub 2017 Jul 13.

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

Author information

1
Department of Internal Medicine F, Hospital Gentofte, Copenhagen University, Copenhagen, Denmark.
2
Department of Biomedical Sciences, NNF Center of Basic Metabolic Research, The Panum Institute, Copenhagen University, Copenhagen, Denmark.

Abstract

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.

KEYWORDS:

dipeptidyl peptidase-4 inhibitors; incretin therapy; type 2 diabetes

PMID:
28544214
DOI:
10.1111/dom.13018
[Indexed for MEDLINE]

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