Research · Evidence roundup

Semaglutide's big outcome trials: SELECT, FLOW, and SOUL explained

By Erik Jones · Oct 20, 2026 · 6 min read

Semaglutide (sold as Ozempic, Wegovy, or Rybelsus) is often described as a drug that “protects the heart and kidneys.” Three large outcome trials are behind that claim: SELECT (2023), FLOW (2024), and SOUL (2025). Here is what each one actually tested, and what it did not.

FLOW: kidney protection, tested in people with type 2 diabetes

FLOW enrolled 3,533 people who had type 2 diabetes and chronic kidney disease, the kind marked by protein leaking into the urine (called albuminuria). Nearly everyone was already taking a standard kidney-protecting blood pressure medicine (an ACE inhibitor or ARB), unless they couldn’t tolerate one. Half were then given semaglutide, 1 mg by injection once a week; the other half got a placebo (a shot with no drug in it).

The trial’s main test was a combined outcome of serious kidney events: kidney failure, a drop in kidney function (eGFR) of at least 50%, or death related to the kidneys or the heart. People on semaglutide had a 24% lower risk of that combined outcome than people on placebo. In the language researchers use, the hazard ratio was 0.76, with a 95% confidence interval of 0.66 to 0.88 — meaning the true effect is very likely somewhere in that range, not just a lucky result.

This is the clearest of the three results for someone with type 2 diabetes and existing kidney disease, because the trial was built around exactly that person.

SOUL: a daily pill, tested in people with type 2 diabetes

SOUL tested the pill form of semaglutide (oral semaglutide, up to 14 mg a day) in 9,650 people aged 50 or older with type 2 diabetes who already had artery disease (in the heart, brain, or legs), chronic kidney disease, or both. Half took the pill, half took a placebo pill, for an average of about four years.

The trial’s main test was a combined heart outcome: death from a cardiovascular cause, a non-fatal heart attack, or a non-fatal stroke. That outcome happened to 12.0% of people on semaglutide versus 13.8% on placebo, a 14% relative reduction (hazard ratio 0.86, 95% CI 0.77 to 0.96). In a supporting analysis of the separate parts — not the trial’s main test — non-fatal heart attacks were about a quarter lower (hazard ratio 0.74), while strokes and cardiovascular deaths on their own did not differ clearly from placebo.

SELECT: a different population — read this part carefully

SELECT is the trial most often quoted alongside the other two, and it is the one that needs the biggest caveat. SELECT enrolled 17,604 people with overweight or obesity (BMI 27 or higher) and existing cardiovascular disease, such as a past heart attack or stroke, who did not have diabetes. Participants took semaglutide 2.4 mg by weekly injection (the dose sold as Wegovy) or a placebo, for an average of a little over three years.

The combined heart outcome, measured the same way as in SOUL, happened 20% less often in the semaglutide group (hazard ratio 0.80, 95% CI 0.72 to 0.90).

That is a real, well-measured result. But SELECT does not show what semaglutide does for a person who has type 2 diabetes, because people with diabetes were excluded from the trial. It describes people without diabetes who have overweight or obesity and cardiovascular disease, which is a different group from the one FLOW and SOUL studied. A 2026 European Society of Cardiology guideline on the management of cardiovascular disease and chronic kidney disease has since been published.

Not medical advice. Educational summary of published research. Last reviewed Oct 27, 2026.