Claimed effect · Semaglutide

Does Semaglutide help with major cardiovascular events?

A
Grade A — established in humans1 large RCT · effect size: moderate
Short answerEstablished in humans. 1 large RCT point the same way: a moderate effect. SELECT trial, 17,604 participants: a 20% relative reduction in people with established cardiovascular disease and no diabetes. A mediation analysis of the trial, published in September 2026, estimated that the measured changes in weight, waist, blood sugar, lipids, blood pressure, inflammation and kidney markers together explain about a third of that reduction (31.4%), with a confidence interval from −30.1% to 143.6% — too wide to say how the drug protects the heart.

What the studies show

SELECT trial, 17,604 participants: a 20% relative reduction in people with established cardiovascular disease and no diabetes. A mediation analysis of the trial, published in September 2026, estimated that the measured changes in weight, waist, blood sugar, lipids, blood pressure, inflammation and kidney markers together explain about a third of that reduction (31.4%), with a confidence interval from −30.1% to 143.6% — too wide to say how the drug protects the heart.

“A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001).”

Verbatim, from the abstractLincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med, 2023;389:2221–2232

Several well-run randomised trials in people, pointing the same way. You can plan around this. It still says nothing about whether the effect is worth the side effects for you.

  1. 1
    Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).N Engl J Med, 2023;389:2221–223217,604 participants; hazard ratio 0.80 for MACE.
  2. 2
    Colhoun HM, et al. Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial.Eur Heart J, 2026 (online Sep 2026)Joint mediation by all measured risk factors 31.4% (95% CI −30.1 to 143.6); the authors conclude the effect cannot be fully ascribed to known risk factors.

In context

Semaglutide is a once-weekly GLP-1 receptor agonist approved for type 2 diabetes and, at a higher dose, for weight management. In large randomised trials it produces roughly 15% average weight loss over 68 weeks and reduces major cardiovascular events in people with existing heart disease. Gastrointestinal side effects are common and are the main reason people stop. It is a prescription medicine; products sold outside that channel are unlicensed copies.

Semaglutide is approved (rx). Legal status differs by country — see the regulation section or the jurisdiction pages.

Questions

Is Semaglutide proven to help with major cardiovascular events?
Yes, as far as human trials can show it: 1 large RCT. LYO grades this outcome A.
What studies are behind the grade?
SELECT trial, 17,604 participants: a 20% relative reduction in people with established cardiovascular disease and no diabetes. A mediation analysis of the trial, published in September 2026, estimated that the measured changes in weight, waist, blood sugar, lipids, blood pressure, inflammation and kidney markers together explain about a third of that reduction (31.4%), with a confidence interval from −30.1% to 143.6% — too wide to say how the drug protects the heart.
Is Semaglutide approved for this?
Semaglutide is an approved medicine (Approved (Rx)); whether this particular outcome is a licensed indication is stated on the compound page's regulation section.

Other outcomes for Semaglutide

Written and maintained by LYO Research — how pages are written and checked. Reviewed 7 October 2026. Grades count human evidence only; see how LYO grades. Not medical advice. Correct this page →