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, P0.001). 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, P0.001). 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.
Watanabe et al. (Sat,) studied this question.