Effect of oral semaglutide on remnant-like lipoprotein cholesterol in patients with ischemic heart disease receiving statin therapy

Shingo Watanabe; Junichi Onuma; Michio Usui

doi:10.1007/s13340-025-00799-w

Effect of oral semaglutide on remnant-like lipoprotein cholesterol in patients with ischemic heart disease receiving statin therapy

Diabetol Int. 2025 Jan 31;16(2):365-371. doi: 10.1007/s13340-025-00799-w. eCollection 2025 Apr.

Authors

Shingo Watanabe¹, Junichi Onuma¹, Michio Usui¹

Affiliation

¹ The Department of Cardiology, Tokyo Yamate Medical Center, 3-22-1 Hyakunincho, Shinjuku-ward, Tokyo, 169-0063 Japan.

PMID: 40166440
PMCID: PMC11954779 (available on 2026-01-31)
DOI: 10.1007/s13340-025-00799-w

Abstract

Objectives: High remnant-like lipoprotein (RLP) cholesterolemia has been reported as a risk factor for cardiovascular events in stable angina patients receiving statin therapy. However, there are no established treatments for lowering RLP cholesterol in patients on statins. Glucagon-Like Peptide-1 (GLP-1) receptor agonists are known to reduce cardiovascular events, but the underlying mechanism is not fully understood. We hypothesized that the lipid profile-improving effects of GLP-1 receptor agonists may also contribute to lowering RLP cholesterol.The purpose of this study was to investigate whether oral semaglutide, a GLP-1 receptor agonist, exerts a cholesterol-lowering effect on RLP cholesterol.

Methods: This study was designed as a single-center, single-group, before-and-after comparison trial. The study population consisted of patients with ischemic heart disease who were receiving statin therapy, had initiated oral semaglutide for diabetes, and had an RLP cholesterol level of 3.9 mg/dL or higher before starting semaglutide (N = 41). RLP cholesterol levels were measured in all patients 3 months after initiating semaglutide therapy. RLP cholesterol levels before and after semaglutide treatment were compared.

Results: After initiating semaglutide, RLP cholesterol levels were significantly lower compared to baseline levels (before 8.52 ± 3.96 mg/dL After 5.46 ± 2.88 mg/dL, P < 0.001). In 21 patients who switched from DPP-4 inhibitors to semaglutide, RLP cholesterol levels also significantly decreased (7.33 ± 1.03 mg/dL → 6.75 ± 0.95 mg/dL, P < 0.001). Additionally, among 30 patients who were already on SGLT-2 inhibitors, RLP cholesterol levels significantly decreased after starting semaglutide (8.01 ± 3.37 mg/dL → 5.42 ± 2.37 mg/dL, P < 0.001). No correlation was observed between the reduction in RLP cholesterol and weight loss.

Conclusions: Oral semaglutide significantly reduced RLP cholesterol levels in patients with ischemic heart disease who were receiving statin therapy.

Keywords: Diabetes; Dyslipidemia; GLP1 receptor agonist; Ischemic heart disease; Oral semaglutide; RLP cholesterol.

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