Differential effect of novel antidiabetic agents on the arterial stiffness and endothelial function in patients with type 2 diabetes mellitus

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<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<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<0.001) in the GLP-1RA group, from 29.9±1.44 to 24.2±1.48% (p<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.