CATEGORY: METABOLIC & BLOOD SUGAR
Adults with type 2 diabetes and established heart or kidney disease who took a once-daily semaglutide tablet were 14% less likely to die of cardiovascular causes or suffer a heart attack or stroke than those given a placebo, in a randomized trial that followed 9,650 people for about four years—12.0% of tablet takers had one of those events, versus 13.8% on placebo.1
A Pill With Something to Prove
Semaglutide belongs to a family of medicines that copy GLP-1, a hormone your gut releases after a meal. The copy works like a longer-lasting version of that natural signal: it prompts the pancreas to release insulin when blood sugar rises, slows the stomach’s emptying, and tells the brain you are full. The injectable forms of these drugs had already shown they protect the heart, but the tablet form—taken by mouth once a day—had never proven in a completed trial that it could do more for the heart than placebo. The SOUL trial was designed to settle exactly that question.1
Four Years, Three Outcomes Counted
Researchers at 444 clinics in 33 countries enrolled 9,650 adults aged 50 and older who had type 2 diabetes along with established cardiovascular disease, chronic kidney disease, or both. Each participant was assigned by chance—neither patients nor doctors knowing who got what—to a daily semaglutide tablet built up to 14 milligrams or to an identical-looking placebo, both added on top of standard diabetes and heart care. For an average of nearly four years, the trial then counted the outcomes that matter most: deaths from cardiovascular causes, nonfatal heart attacks, and nonfatal strokes.1
Twelve of a Hundred, Instead of Nearly Fourteen
By the end of follow-up, 579 of the 4,825 people on the tablet (12.0%) had died of a cardiovascular cause or had a heart attack or stroke, compared with 668 of the 4,825 on placebo (13.8%)—a 14% lower risk. Picture a waiting room holding a hundred patients like these: over four years, roughly fourteen of them would be expected to have one of those events without the tablet, and twelve with it. Measured another way, events occurred at a rate of 3.1 per 100 person-years with semaglutide versus 3.7 with placebo.1
The Kidneys Did Not Follow the Heart
The trial did not deliver on everything it measured. Major kidney disease events—one of its planned confirmatory secondary outcomes—occurred at rates that did not differ significantly between the groups, so the tablet’s win was a heart result, not a kidney one. Safety, meanwhile, held up: serious adverse events were no more common with semaglutide than with placebo.1
The Injectable Story, Retold by Mouth
The result fits a consistent pattern from randomized trials of the same molecule given as a weekly injection. In a trial of 17,604 adults who had cardiovascular disease and a higher body weight but no diabetes, injectable semaglutide cut the same composite of cardiovascular death, heart attack and stroke by 20%—6.5% of participants versus 8.0% on placebo.2 What the new trial adds is the formulation: the heart protection seen with the injections showed up with a daily tablet as well, in a population with diabetes at high cardiovascular risk.
Key Takeaways
- In a four-year randomized trial of 9,650 adults with type 2 diabetes and established heart or kidney disease, a once-daily semaglutide tablet lowered the combined risk of cardiovascular death, heart attack and stroke by 14%—12.0% versus 13.8% with placebo.
- Because participants were assigned by chance, the result carries causal weight: the tablet, not differences between the people taking it, made the difference.
- The benefit did not extend to major kidney disease events, which occurred at similar rates in both groups, and serious adverse events were no more common on the tablet.
- The finding matches the 20% reduction seen with injectable semaglutide in a separate randomized trial, extending the heart benefit of this drug family to its pill form.
References
- McGuire DK, Marx N, Mulvagh SL, et al. Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. New England Journal of Medicine. 2025;392(20):2001–2012. link
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine. 2023;389(24):2221–2232. link