CATEGORY: METABOLIC & BLOOD SUGAR
A once-daily semaglutide tablet lowered the risk of cardiovascular death, heart attack or stroke by 14% in adults who had type 2 diabetes along with established heart or kidney disease. Over about four years, 12.0% of the 9,650 people in the trial who took the tablet had one of those events, against 13.8% of those 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 behaves 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 signals fullness to the brain. Injectable forms had already shown they protect the heart. The tablet had not: no completed trial had established that a daily pill could do more for the heart than placebo. SOUL was designed to settle that. Researchers at 444 clinics in 33 countries enrolled 9,650 adults from age 50 upward, each carrying type 2 diabetes plus established cardiovascular disease, chronic kidney disease, or both. Allocation to a daily semaglutide tablet built up to 14 milligrams, or to an identical-looking placebo, came from a blinded randomization list; both went on top of standard diabetes and heart care. For an average of nearly four years the trial then counted 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 cardiovascular causes or suffered a heart attack or stroke, against 668 of the 4,825 on placebo (13.8%). That is a 14% lower risk. Picture a waiting room holding a hundred patients like these. Over four years, roughly fourteen would be expected to have one of those events without the tablet, and twelve with it. Counted another way, events came at 3.1 per 100 person-years with semaglutide versus 3.7 on placebo. The kidneys did not follow the heart. Major kidney disease events, one of the planned confirmatory secondary outcomes, occurred at rates that did not differ significantly between the groups, so the win was a heart result and not a kidney one. Safety held: serious adverse events were no more common on semaglutide than on 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. Among 17,604 adults who had cardiovascular disease and a higher body weight but no diabetes, injectable semaglutide cut the same combination of cardiovascular death, heart attack and stroke by 20%, from 8.0% of participants on placebo to 6.5% on the drug.2 What the new trial adds is the formulation. Heart protection that had shown up with injections showed up with a daily tablet too, this time in people with diabetes at high cardiovascular risk.
Key Takeaways
- Over four years, a once-daily semaglutide tablet lowered the combined risk of cardiovascular death, heart attack and stroke by 14% in 9,650 adults with type 2 diabetes and established heart or kidney disease, 12.0% versus 13.8% on placebo.
- A random, blinded allocation is what gives the result its causal weight: the tablet, rather than differences between the people taking it, produced the gap.
- Major kidney disease events came out the same in both groups, and serious adverse events were no more common on the tablet.
- A separate randomized trial of injectable semaglutide produced a 20% reduction, which puts this drug family’s heart benefit in pill form as well.
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