Oral semaglutide reduces MACE in patients with T2D and ASCVD and/or CKD
ACC.25 – In SOUL, treatment with oral semaglutide versus placebo reduced the risk of MACE by 14% in patients with T2D and ASCVD, CKD or both.
This summary is based on the presentation of Darren McGuire, MD (Dallas, TX, USA) at the ACC.25 Scientific Session - Oral Semaglutide Reduces Cardiovascular Events in People with Type 2 Diabetes with Atherosclerotic Cardiovascular and/or Chronic Kidney Disease: Primary Results From the SOUL Randomized Trial.
Introduction and methods
The injectable GLP-1RA semaglutide reduces CV risk in patients with T2D and with CVD or high CVD risk. Many patients are hesitant to use injection therapies and prefer oral formulations. It remains unclear whether the oral formulation of semaglutide has beneficial cardiovascular effects in high-risk patients with T2D. The objective of the SOUL trial was to investigate the cardiovascular efficacy of oral semaglutide versus placebo with regards to MACE in persons with T2D and at high risk of CV events.
The SOUL (Semaglutide Cardiovascular Outcomes Trial) trial was a double-blind, randomized, placebo-controlled, event-driven superiority trial, in which 9650 patients (≥50 years) with T2D, HbA1c 6.5-10.0% and ASCVD and/or CKD were randomized to once-daily oral semaglutide (14 mg) or placebo on top of standard of care. The median follow-up period was 49.5 months.
The primary outcome was 3-point MACE, defined as a composite of CV death, nonfatal MI or nonfatal stroke. If this was significant, further hierarchy testing was performed. The first confirmatory secondary outcome was a 5-point composite kidney outcome, defined as a composite of CV death, kidney death, persistent ≥50% eGFR reduction, persistent eGFR <15 mL/min/1.73m² or chronic kidney replacement therapy.
Main results
- Oral semaglutide reduced the risk of the primary outcome compared with placebo (HR: 0.86; 95%CI: 0.77–0.96; P=0.0028 for superiority).
- The effect of oral semaglutide on 3-point MACE was consistent regardless of sex, age, BMI, eGFR and SGLT2i at baseline.
- The 5-point composite kidney outcome occurred in 403 patients in the oral semaglutide group and in 435 patients in the placebo group (HR: 0.91; 95%CI: 0.80–1.05; P=0.0967).
- The reductions in HbA1c and body weight were consistent with previous trial findings.
- The safety profile of oral semaglutide in SOUL was comparable with previous studies with semaglutide.
Conclusion
In the SOUL trial among patients with T2D and ASCVD and/or CKD, oral semaglutide reduced the risk of MACE compared with placebo. This beneficial effect was consisted across various subgroups. “Oral semaglutide is the first and only oral GLP-1RA with proven cardiovascular benefits,” said Darren McGuire.
- Our reporting is based on the information provided at the ACC.25 Scientific Session -