JAMA Cardiol
Oral semaglutide shows sustained improvements in multiple cardiovascular risk factors
Clinical takeaway: Oral semaglutide demonstrated early and durable improvements across multiple cardiovascular risk factors — including HbA1c, body weight, systolic blood pressure, hsCRP, and triglycerides — on top of standard-of-care therapy, suggesting its reduction in MACE (major adverse cardiovascular events -- a composite of cardiovascular death, nonfatal MI, and nonfatal stroke) may stem from cumulative risk factor modification rather than any single mechanism.
In this post hoc secondary analysis of the SOUL trial (N=9,650; mean age 66 years), oral semaglutide 14 mg daily was associated with significant reductions compared with placebo in HbA1c (−0.47 percentage points), body weight (−3.26%), systolic blood pressure (−1.83 mm Hg), hsCRP (−23%), non-HDL cholesterol (−2%), and triglycerides (−6%) at week 156. Improvements appeared as early as week 13 and were sustained throughout the trial. No significant differences were observed for LDL cholesterol or diastolic blood pressure. The authors note that while individual changes were modest, their collective impact may underlie the observed 14% reduction in MACE.
Source:
Mulvagh SL, et al. (2026, March 25). JAMA Cardiol. 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. https://jamanetwork.com/journals/jamacardiology/fullarticle/2847041
