Spectrum of effects of dipeptidyl peptidase-4 inhibitors: within and beyond glycemic control (part 1)
Year: 2025
Type: article
Abstract: The current focus of type 2 diabetes mellitus (T2DM) control has shifted from HbA1c to glycemic variability (GV) due to its key role in the accelerated development of diabetic complications, in addition to chronic hyperglycemia. The central link in the early stage of dysglycemia is β-cell dysfunction with subsequent loss of their mass with an important role of hyperglucagonemia at all stages of the diabetic continuum. Coordinated work of α and β-cells with the help of two endogenous incretins: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) is of decisive importance for maintaining glucose homeostasis. The ability of dipeptidyl peptidase-4 (DPP-4) inhibitors to not only maintain β-cell mass and promote insulin release, but also simultaneously correct glucagon secretion from α-cells, preventing hypoglycemia, by preserving bioactive GLP-1 and GIP intact, attracts special attention to these drugs. The place of DPP-4 inhibitors among various pharmacological treatment options for T2DM is considered: details of glycemic control and the role in reducing GV with safety in relation to the risk of cardiovascular diseases (CVD) are clarified. New data on the mechanisms of action of dipeptidase-4 are presented, which, as a new adipokine with systemic activity and cellular specificity in the regulation of not only metabolic homeostasis, but also inflammatory processes, may represent a key link between central obesity, insulin resistance (IR) and atherosclerosis. Accordingly, the pathophysiological relationship between T2DM and CVD through IR and low-level inflammation has determined a shift in therapy goals from blood glucose control to general risk factor management, which clarifies the role and place of DPP-4 inhibitors.
Source: Diabetes Mellitus
DOI: 10.14341/dm13342
Authors: L. A. Ruyatkina, D. S. Ruyatkin
Institution: Novosibirsk State Medical University
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4415031636