Key Takeaways
- In a new analysis of the 9,650-person SOUL trial, oral semaglutide produced 683 total major cardiovascular events versus 791 on placebo — a 14% lower total burden.
- The benefit covers first events; the effect on second events alone was not statistically significant, and the analysis is exploratory.
- The trial covered only people with type 2 diabetes plus heart or kidney disease, and was funded by the drug's maker, Novo Nordisk.
First Heart Attacks Get the Headlines. This Study Counted the Second Ones Too
Most heart-drug trials stop counting at a patient's first heart attack or stroke. A new analysis of the SOUL trial, published in JAMA Cardiology, counted everything — first events and every one after — and found the daily diabetes pill oral semaglutide lowered the total toll.
Across 9,650 people with type 2 diabetes and existing heart or kidney disease, followed for about four years, the semaglutide group recorded 683 major cardiovascular events in total — heart attacks, strokes and cardiovascular deaths, first and subsequent combined. The placebo group recorded 791. That is a mean ratio of 0.86, a 14% lower total event burden.
Why the total count matters
For patients, a second heart attack is not a footnote to the first — it is often the more dangerous one. SOUL's original result already showed the pill cut first events. This prespecified follow-up analysis asks whether protection holds across the whole course of illness, and on the combined count, it does: including non-cardiovascular deaths in the tally, there were 138 fewer events on the drug (910 versus 1,048).
The honest limits
Three cautions belong with the headline. The trial "was not designed to test for treatment differences in subsequent events," the authors note — so when second events are isolated on their own, the difference (hazard ratio 0.85) is not statistically significant, and the analysis involved no adjustment for multiple comparisons. The population was high-risk by design: type 2 diabetes plus atherosclerotic heart disease and/or chronic kidney disease — this says nothing about people outside that group. And the trial was funded by Novo Nordisk, the drug's maker, which also ran the statistics. Side effects led 15.5% of the semaglutide group to stop the drug, versus 11.6% on placebo.
The Twikup Take
Counting only first events flatters every heart drug a little, because real patients keep having events. This analysis holds up reasonably well under the stricter count — with the exploratory label and the maker's money both on the table, where they belong.
Image: Illustrative image.