A new phase 3b trial found that the oral formulation of semaglutide, a GLP-1 receptor agonist, reduces the risk for major adverse cardiovascular events in patients with type 2 diabetes and established atherosclerotic cardiovascular disease or chronic kidney disease. The study, SOUL, involved over 9,650 patients and showed a 14% relative reduction in cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke after a mean follow-up of 49.5 months.
The results are consistent with previous studies on injectable semaglutide and other GLP-1 receptor agonists. The study’s principal investigator, Darren K. McGuire, noted that the oral agent is “proof of benefit” for addressing an unmet clinical need in type 2 diabetes patients with cardiovascular disease.
While the trial found a significant reduction in cardiovascular events, it did not show a statistically significant kidney protection benefit. However, other secondary outcomes showed that semaglutide reduced nonfatal stroke and major adverse limb events.
A substudy of patients taking sodium-glucose cotransporter-2 (SGLT2) inhibitors also found that the oral semaglutide formulation was effective in reducing cardiovascular risk regardless of SGLT2 inhibitor use. This is a significant finding, as it suggests that the oral agent can be used independently of other treatments.
The results have implications for prescribing oral semaglutide to patients with type 2 diabetes and concomitant cardiovascular disease. While the study’s findings are promising, McGuire noted that some prescribers may still hesitate to prescribe the medication due to concerns about injection administration. However, he emphasized that injectable semaglutide is a highly effective treatment option for many patients.
Source: https://www.medscape.com/viewarticle/oral-glp-1-receptor-antagonist-reduces-cv-risk-2025a10007kr?form=fpf