Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial.
SOUL is a large randomized, double-blind, placebo-controlled cardiovascular outcomes trial of oral semaglutide 14 mg daily versus placebo in 9650 people with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease.
Background
Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist. SOUL (Semaglutide cardiOvascular oUtcomes triaL) was designed to assess its effect on the risk of cardiovascular events in individuals with type 2 diabetes who have established atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or both.
Study design
SOUL is a randomized, double-blind, parallel-group, placebo-controlled cardiovascular outcomes trial comparing oral semaglutide 14 mg once daily with placebo, both added to standard of care, in individuals aged 50 years or older with type 2 diabetes and evidence of ASCVD (coronary artery disease, cerebrovascular disease, or symptomatic peripheral arterial disease) and/or CKD (eGFR below 60 mL/min/1.73 m2). The primary outcome is time to first major adverse cardiovascular event, a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; the event-driven trial continued until 1225 confirmed events occurred.
Key findings
Overall, 9650 participants were enrolled between June 2019 and March 2021 (71.1% men, mean age 66.1 years, mean diabetes duration 15.4 years, mean HbA1c 8.0%). At randomization, 70.7% had coronary artery disease, 42.3% had CKD, 21.1% had cerebrovascular disease, and 15.7% had symptomatic peripheral arterial disease (categories not mutually exclusive), and 23.0% had heart failure. Common baseline antihyperglycaemic agents included metformin (75.7%), insulin (50.5%), and SGLT2 inhibitors (26.7%).
Clinical implications
SOUL was positioned to provide evidence on the cardiovascular effects of oral semaglutide in a high-risk population with type 2 diabetes and established ASCVD and/or CKD. The subsequently reported primary results showed oral semaglutide lowered the risk of major adverse cardiovascular events compared with placebo (hazard ratio 0.86; 95% CI 0.77-0.96) without an increase in serious adverse events.
Category
Research
Source
Diabetes Obes Metab
More from ASNRT News
Browse the latest news, society announcements, KDIGO guideline updates, and AJNT issue releases on the ASNRT newsroom.