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Abstract

Background/Introduction

Type-2 diabetes mellitus (T2DM) is associated with endothelial and arterial dysfunction.

Purpose

We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i)and their combination on endothelial and arterial function of T2DM patients.

Methods

A hundred-sixty T2DM patients (age: 58±10 years) were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40)as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25μm) using Sideview Darkfield imaging. Increased PBR indicates reduced glucocalyx thickness, b) pulse wave velocity (PWV-Complior), central systolic blood pressure (cSBP) and augmentation index (AI) of the aortic pulse wave.

Results

Twelve months post-treatment, all patients improved PBR, PWV and AI (p<0.05). GLP-1RA, SGLT-2i and their combination showed a greater reduction of PBR, PWV and cSBP than insulin, despite a similar HbA1c reduction (p<0.05). SGLT-2i or combined therapy with GLP-1RA and SGLT-2i showed a greater decrease of PWV (−10.1% and −13% vs. −3.6% and −8.6%) and cSBP (−3% and −5.5% vs. −0.8% and −1.5%)than insulin or GLP-1RA (p<0.05 for all comparisons). GLP-1RA or GLP-1RA+SGLT-2i provided a greater decrease of AI (−42.7% and −48.6% vs. +6.2% vs. −3.8%) compared with insulin or SGLT-2i (Table). The dual therapy showed the greatest effect on measured markers in patients with LVEF <55% (p<0.05).

Conclusions

Twelve-month treatment with SGLT-2i and its combination with GLP-1RA, showed a greater improvement on arterial elastic properties than GLP1RA or insulin treatment in T2DM. The combined therapy as second line was superior to either insulin, or GLP-1RA and SGLT-2i separately.

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Table 1

All patients (n=160)Insulin (n=40)GLP-1RA (n=40)SGLT-2i (n=40)GLP-1RA+SGLT-2i (n=40)p-value
PBR, 5–25μmBaseline2.13±0.32.13±0.32.1±0.292.15±0.32.16±0.290.653
4 months2.14±0.32.15±0.32.07±0.32.19±0.32.12±0.320.220
12 months2.05±0.32.10±0.32.04±0.22.08±0.21.98±0.30.037
PWV, m/sBaseline11.8±2.711.5±2.711.6±2.812±2.812.3±2.60.263
4 months11.5±2.611.5±2.711.4±2.511.4±2.411.5±2.60.860
12 months10.8±211.1±2.310.5±1.910.9±2.110.8±20.021
AI, %Baseline12 (2–23)13.6 (1–25)12.7 (3–25)10.8 (2–19)11 (1–21)0.740
4 months10.8 (0–21)14.1 (4–23)10.8 (0–21)10 (2–19)8.3 (0–18)0.190
12 months10.3 (1–22)14.5 (3–24)8.9 (-2–18)10.4 (3–24)7.4 (0–19)0.041
All patients (n=160)Insulin (n=40)GLP-1RA (n=40)SGLT-2i (n=40)GLP-1RA+SGLT-2i (n=40)p-value
PBR, 5–25μmBaseline2.13±0.32.13±0.32.1±0.292.15±0.32.16±0.290.653
4 months2.14±0.32.15±0.32.07±0.32.19±0.32.12±0.320.220
12 months2.05±0.32.10±0.32.04±0.22.08±0.21.98±0.30.037
PWV, m/sBaseline11.8±2.711.5±2.711.6±2.812±2.812.3±2.60.263
4 months11.5±2.611.5±2.711.4±2.511.4±2.411.5±2.60.860
12 months10.8±211.1±2.310.5±1.910.9±2.110.8±20.021
AI, %Baseline12 (2–23)13.6 (1–25)12.7 (3–25)10.8 (2–19)11 (1–21)0.740
4 months10.8 (0–21)14.1 (4–23)10.8 (0–21)10 (2–19)8.3 (0–18)0.190
12 months10.3 (1–22)14.5 (3–24)8.9 (-2–18)10.4 (3–24)7.4 (0–19)0.041
Funding Acknowledgement

Type of funding source: None

Peripheral Vascular and Cerebrovascular Disease: Pharmacotherapy
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