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Effects of semaglutide on cardiovascular outcomes in very elderly patients with acute coronary syndrome and type 2 diabetes: a real-world study

cardiology
diabetes-and-endocrinology
geriatrics
endocrinology
diabetes

Abstract

Abstract
Background
Previous studies have established that semaglutide reduces the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). The risk of MACE is markedly increased in very elderly (≥75 years) patients with T2DM and acute coronary syndrome (ACS). However, real-world evidence regarding the effectiveness and safety of semaglutide in this specific population remains limited. This study aims to address this evidence gap.
Methods
This study is a retrospective cohort analysis that included very elderly patients diagnosed with ACS and T2DM who were treated at the First Affiliated Hospital of Xinjiang Medical University between October 2021 and June 2025. Based on long-term (>6 months) use of semaglutide, patients were divided into a semaglutide group (n=317) and a control group (n=402). Baseline clinical characteristics, physical examination findings, and laboratory indicators were collected for both groups. The primary outcome was a composite endpoint (MACE) consisting of non-fatal myocardial infarction, non-fatal stroke, heart failure, cardiac-related rehospitalization, and cardiovascular death. Survival curves were plotted using the Kaplan-Meier method, and a multivariable Cox proportional hazards regression model was employed to assess the effect of semaglutide on the risk of MACE in this high-risk population.
Results
A total of 719 patients were enrolled in this study, with a median follow-up of 17.9 months (ranging from 12.5 to 22.4 months). Compared to the control group, the semaglutide group showed significant reductions in total cholesterol, triglycerides, low-density lipoprotein cholesterol, glycated hemoglobin, body mass index, C-reactive protein, and NT-proBNP levels, as well as a slower decline in left ventricular ejection fraction (all p < 0.05). The cumulative incidence of MACE was 202 cases (63.7%) in the semaglutide group and 248 cases (61.7%) in the control group. In multivariable Cox proportional hazards model 3, the semaglutide group demonstrated a 40% reduction in MACE risk compared to the control group (Hazard Ratio [HR] 0.60, 95% confidence interval [CI] 0.48-0.75; p < 0.001). Significant reductions were also observed in secondary endpoints including unplanned revascularization (HR = 0.36, 95% CI 0.18-0.75, p = 0.006) and recurrent myocardial infarction (HR = 0.31, 95% CI 0.13-0.73, p = 0.007).
Conclusions
In very elderly patients with T2DM and ACS, treatment with semaglutide is associated with a significant reduction in MACE risk, along with notable improvements in metabolic, inflammatory, and cardiac function parameters.
Keywords
ACS;T2DM;Semaglutide;Very Elderly Patients;MACE
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