Differential effect of novel antidiabetic agents on the arterial stiffness and endothelial function in patients with type 2 diabetes mellitus
Authors: Stampouloglou P K , Bletsa E , Siasos G , Oikonomou E , Paschou S A , Gouliopoulos N , Katsianos E , Tsigou V , Kassi E , Tentolouris N , Tsioufis K , Tousoulis D 
Published: October 2021

Abstract

Background
Arterial stiffness and endothelial function markers flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM).

Purpose
To investigate the effects of novel antidiabaetic agents on arterial stiffness and endothelial function in T2DM patients.

Patients and methods
We enrolled 80 consecutive patients under stable antidiabetic therapy who did not reach therapeutic targets. Subjects were assessed to receive an additional antidiabetic agent to optimize glucose control; dipeptidyl peptidase-4 inhibitor (DPP-4i, n=24), glucagon like peptide-1 receptor agonist (GLP-1RA, n=26), sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=21) or long lasting insulin (n=9). Glycosylated hemoglobin (Hba1c) along with carotid-femoral pulse wave velocity (PWV), augmentation index (Alx) and flow-mediated dialatation (FMD), as biomarkers of arterial stiffness and endothelial function accordingly, were measured at baseline and 3 months after treatment intensification.

Results
There were no differences between the study groups in traditional risk factors, or baseline HbA1c, PWV, Alx and FMD levels (ps=NS for all). All groups achieved better glycemic control in terms of HbA1c values between baseline and follow-up, as seen in the paired differences of these values (for DPP4i: 0.7±0.3%, for GLP-1RA: 1.3±0.7%, for SGLT-2i: 0.8±0.5% and for insulin 2.0±0.8%, p&lt;0.001 for all). PWV showed a decrease from 10.0±0.84 to 9.1±0.43 m/sec (p=0.092) in the DPP4-i group, from 11.7±0.72 to 10.2±0.74 m/sec (p&lt;0.001) in the GLP-1RA group, from 10.3±0.54 to 9.6±0.59 m/sec (p=0.001) in the SGLT-2i group and from 11.6±1.04 to 11.1±1.02 m/sec (p=0.219) in the insoulin group, as presented in Figure 1. Alx was also decreased from 34.2±1.89 to 31.5±2.7% (p=0.023) in the DPP-4i group, from 29.1±1.52 to 25.6±2.09% (p&lt;0.001) in the GLP-1RA group, from 29.9±1.44 to 24.2±1.48% (p&lt;0.001) in the SGLT-2i group and from 28.2±2.33 to 26.2±1.64% (p=0.153) in the insulin group, as presented in Figure 1, as well. Regarding FMD, a reduction in the values between groups from baseline to follow-up was also observed; from 5.33±1.3 to 5.50±1.1% (p=0.004) for the DPP-4i group, from 5.54±0.8 to 5.99±0.8% (p=0,001) for the GLP-1RA group, from 5.59±0.9 to 5.77±1.2% (p=0.005) for the SGLT-2i group and from 5.76±0.8 to 5.83±0.9% for the insulin group, as demonstrated in Figure 2.
Limitations: Our results should be examined under the scope of limited data pool and its subsequent restrictions.

Conclusion
These preliminary data provide evidence that treatment intesification- particularly with GLP1-RA and SGLT-2i, benefits vascular properties, a finding which could partly explain the positive cardiovascular outcomes of recent randomized clinical trials in this field.

Funding Acknowledgement
Type of funding sources: None.