Cardiometabolic & kidneySecondary analysis
Oral Semaglutide and Change in Cardiovascular Risk Factors in High-Risk Type 2 Diabetes
- Secondary analysis of the SOUL randomised trial
- post hoc
- intention-to-treat
- double-blind
- multicentre
Randomisation June 2019 to March 2021; mean (SD) follow-up 47.5 (10.9) months
Authors' conclusion
In this post hoc secondary analysis of the SOUL randomized clinical trial, oral semaglutide was associated with early and sustained improvements vs placebo in multiple ASCVD risk factors in high-risk participants with T2D and ASCVD and/or CKD, incremental to SoC.
Study context
- Population
- Adults with T2DM and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD) receiving standard of care9,495 (98.4%) completed
- Participants
- 9,650 adults
- Comparison
- Oral semaglutide vs placebo
- Primary endpoint
- Change in HbA1c, body weight and blood pressure (BP) (estimated treatment differences) and hsCRP and lipid levels (estimated treatment ratios)
- Follow-up
- Week 156
Primary result
As reported in the abstract
ASCVD risk factors
Oral semaglutide vs PlaceboETD, percentage points (95% CI)
HbA1c
−0.47(−0.52 to −0.42)
body weight
−3.26(−3.55 to −2.98)
Oral semaglutide vs PlaceboETD, mm Hg (95% CI)
SBP
−1.83(−2.47 to −1.18)
pulse pressure
−2.17(−2.72 to −1.61)
ETR
- High-sensitivity C-reactive protein (hsCRP)
- 0.77 (95% CI 0.74–0.81)
- total cholesterol
- 0.99 (95% CI 0.98–1.00)
- non-HDL-C
- 0.98 (95% CI 0.97–0.99)
- HDL-C
- 1.01 (95% CI 1.01–1.02)
- triglycerides
- 0.94 (95% CI 0.93–0.96)
Further findings
Early risk-factor changes vs placebo · 13 weeks
- HbA1c
- −0.87 percentage points
- Body weight
- −2.54%
- Systolic BP (SBP)
- −3.84 mm Hg
- Pulse pressure
- −3.81 mm Hg
- hsCRP
- −18.08%
- Total cholesterol
- −7.00%
- Non-HDL-C
- −8.02%
- HDL-C
- −4.49%
- Triglycerides
- −8.15%
- sustained over the trial duration
Original publication
Oral Semaglutide and Change in Cardiovascular Risk Factors in High-Risk Type 2 Diabetes. JAMA Cardiol. Published 1 May 2026. doi:10.1001/jamacardio.2026.0245
Summarised from the published abstract; every number is checked against it