Oral Semaglutide Improves ASCVD Risk Factors in High-Risk T2D Patients: Study

A recent post hoc analysis published the Journal of the American Medical Association revealed oral semaglutide to show early and sustained improvements in multiple atherosclerotic cardiovascular disease (ASCVD) risk factors when compared to placebo in high-risk patients with type 2 diabetes (T2D) and coexisting ASCVD and/or chronic kidney disease (CKD), providing benefits beyond standard of care.

People with T2D face a significantly elevated risk of ASCVD, often compounded by conditions such as CKD. Controlling blood sugar, blood pressure, cholesterol levels, and systemic inflammation helps in managing this risk. The latest findings suggest that oral semaglutide may contribute meaningfully across several of these areas.

The analysis included 9,650 adults with T2D and established ASCVD and/or CKD, all who received standard of care treatment. Participants were randomized to receive either once-daily oral semaglutide (up to 14 mg) or a placebo and were followed for an average of nearly 4 years. Also, over 98% of participants completed the trial, strengthening the reliability of the findings.

This research observed that improvements in several cardiovascular risk markers appeared as early as 13 weeks after starting semaglutide and were sustained throughout the study period. These included reductions in glycated hemoglobin (HbA1c), body weight, systolic blood pressure, and pulse pressure. Markers of inflammation and lipid metabolism also improved, including decreases in high-sensitivity C-reactive protein (hsCRP), total cholesterol, and triglycerides.

By week 156, participants taking semaglutide continued to show statistically significant advantages over the placebo group. HbA1c levels were reduced by nearly half a percentage point, body weight by over 3%, and systolic blood pressure by close to 2 mm Hg. Inflammatory markers remained lower, and lipid profiles showed modest but favorable shifts, particularly in non–HDL cholesterol and triglycerides.

LDL cholesterol and diastolic blood pressure did not show significant differences between the two groups. However, the overall pattern suggests a consistent and sustained benefit across multiple risk factors associated with cardiovascular disease. Overall, the findings highlight that the cardiovascular protection offered by oral semaglutide may extend beyond its glucose-lowering effects.

Source:

Mulvagh, S. L., Inzucchi, S. E., Marx, N., Poulter, N. R., Deanfield, J. E., Pop-Busui, R., Emerson, S. S., Mann, J. F. E., Engelmann, M. D. M., Hovingh, G. K., Mandavya, K., Davicevic-Elez, Z., Jeppesen, O. K., Lorenzatti, A., Oguz, A., Mankovsky, B., Deerochanawong, C., Gorgojo-Martinez, J. J., Ji, L., … Murray, A. V. (2026). Oral semaglutide and change in cardiovascular risk factors in high-risk type 2 diabetes: A post hoc secondary analysis of the SOUL randomized clinical trial. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2026.0245