SOUL
Trial question
What is the effect of oral semaglutide in patients with T2DM and ASCVD and/or CKD?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
29.0% female
71.0% male
N = 9650
9650 patients (2790 female, 6860 male).
Inclusion criteria: adult patients, aged ≥ 50 years, with T2DM and ASCVD and/or CKD.
Key exclusion criteria: ESRD; receipt of long-term RRT; MI, stroke, hospitalization for unstable angina pectoris or TIA within the past 60 days; planned coronary, carotid, or peripheral artery revascularization; treatment with any GLP-1 receptor agonist within the past 30 days.
Interventions
N=4825 semaglutide (3 mg once daily as starting dose, with a maximum dose of 14 mg, plus standard care).
N=4825 placebo (matching placebo PO plus standard care).
Primary outcome
Major adverse CV events
12%
13.8%
13.8 %
10.4 %
6.9 %
3.5 %
0.0 %
Semaglutide
Placebo
Significant
decrease ▼
NNT = 55
Significant decrease in major adverse CV events (12% vs. 13.8%; HR 0.86, 95% CI 0.77 to 0.96).
Secondary outcomes
No significant difference in major kidney disease events (8.4% vs. 9%; HR 0.91, 95% CI 0.8 to 1.05).
No significant difference in CV death (6.2% vs. 6.6%; HR 0.93, 95% CI 0.8 to 1.09).
Significant decrease in major adverse limb events (1.5% vs. 2.1%; HR 0.71, 95% CI 0.52 to 0.96).
Safety outcomes
No significant difference in acute pancreatitis.
Significant difference in serious adverse events (47.9% vs. 50.3%).
Conclusion
In adult patients, aged ≥ 50 years, with T2DM and ASCVD and/or CKD, semaglutide was superior to placebo with respect to major adverse CV events.
Reference
Darren K McGuire, Nikolaus Marx, Sharon L Mulvagh et al. Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. N Engl J Med. 2025 Mar 29. Online ahead of print.
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