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Oral semaglutide was efficacious and safe in patients with type 2 diabetes and atherosclerotic vascular disease and/or chronic kidney disease in the phase 3b SOUL trial. This is the first oral GLP-receptor antagonist that delivered cardiovascular benefits for patients with type 2 diabetes in a phase 3 study.

The phase 3b SOUL trial (NCT03914326) randomly assigned 9,650 patients of at least 50 years of age with type 2 diabetes and atherosclerotic vascular disease and/or chronic kidney disease 1:1 to oral semaglutide plus standard-of-care or a placebo plus standard-of-care. The primary endpoint was a 3-point major cardiovascular adverse event outcome, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Darren McGuire, MD, University of Texas, TX, presented the study’s primary results.

After approximately 4.5 years of follow-up, oral semaglutide had met the primary endpoint (HR 0.86; 95% CI 0.77–0.96; P=0.0028). “This finding reflects an absolute risk reduction of 2% over 3 years,” added Dr. McGuire. Other outcomes favored semaglutide numerically but not significantly (5-point major kidney disease events composite HR 0.91; 95% CI 0.80–1.05; and cardiovascular death HR 0.93; 95% CI 0.80–1.09). Oral semaglutide did seem to offer a benefit in terms of major adverse limb events (HR 0.71; 95% CI 0.52–0.96). “This hypothesis-generating result needs to be investigated in further studies,” according to Dr. McGuire. Lastly, Dr. McGuire mentioned that the safety profile of semaglutide in the SOUL trial was similar to that observed in previous semaglutide clinical trials.

Thus, oral semaglutide outperformed placebo for the reduction of cardiovascular events in patients with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease.

Medical writing support was provided by Robert van den Heuvel.
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