# Once-Weekly Semaglutide Is Associated With Improvement in Vascular Endothelial Function in Patients With Type 2 Diabetes Mellitus: A Retrospective Observational Study

**Authors:** Seigo Sugiyama, Akira Yoshida, Noboru Kurinami, Kunio Hieshima, Katsunori Jinnouchi, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Hideaki Jinnouchi

PMC · DOI: 10.7759/cureus.99998 · Cureus · 2025-12-24

## TL;DR

A study found that once-weekly semaglutide improves vascular function in Japanese patients with type 2 diabetes, suggesting cardiovascular benefits.

## Contribution

This is the first study to show semaglutide's improvement in vascular endothelial function in Japanese T2DM patients.

## Key findings

- Semaglutide significantly improved vascular endothelial function as measured by RHI.
- Semaglutide reduced body weight, HbA1c, and LDL cholesterol in T2DM patients.
- Improvements in vascular function were not correlated with changes in metabolic parameters.

## Abstract

Background: Patients with type 2 diabetes mellitus (T2DM) have a high-risk condition of developing cardiovascular disease, and therefore, therapeutic strategies should consider cardiovascular risk reduction. Previously, we demonstrated that circulating glucagon-like peptide-1 (GLP-1) levels are significantly lower in Japanese patients with coronary artery disease (CAD) compared with non-CAD subjects. Once-weekly semaglutide, a GLP-1 receptor agonist, has demonstrated clinical cardiometabolic benefits; however, its effect on vascular endothelial function in Japanese patients with T2DM remains unclear.

Methods: This retrospective observational study included patients with T2DM who were hospitalized at Jinnouchi Hospital and initiated once-weekly subcutaneous semaglutide therapy since 2021. Vascular endothelial function was assessed using reactive hyperemia peripheral arterial tonometry, expressed as the reactive hyperemia index (RHI), before and after semaglutide treatment. Clinical parameters including body weight (BW), glycated hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-cho), and high-sensitivity C-reactive protein (hsCRP) were also evaluated.

Results: A total of 24 patients (mean age: 55 years; n=20 (83.3%) male) were included. RHI significantly increased following semaglutide therapy (baseline: 1.62±0.19 versus follow-up: 2.04±0.60; p<0.01). BW, HbA1c, and LDL-cho also showed significant reductions (all p<0.01). HsCRP tended to decrease, though not significantly. None of the changes in BW, HbA1c, LDL-cho, or hsCRP correlated with the changes in RHI.

Conclusion: Once-weekly semaglutide treatment significantly provided potential improvement in vascular endothelial function in Japanese patients with T2DM, supporting the cardiovascular protective role of semaglutide therapy in the clinical management of T2DM.

## Linked entities

- **Proteins:** GCG (glucagon)
- **Chemicals:** semaglutide (PubChem CID 56843331)
- **Diseases:** type 2 diabetes mellitus (MONDO:0005148), T2DM (MONDO:0005148), coronary artery disease (MONDO:0005010), CAD (MONDO:0005010)

## Full-text entities

- **Genes:** GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}
- **Diseases:** T2DM (MESH:D003924), cardiovascular disease (MESH:D002318), CAD (MESH:D003324)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12831498/full.md

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Source: https://tomesphere.com/paper/PMC12831498