In Adults With Obesity and Heart Disease, Semaglutide Cut Serious Heart Events

CATEGORY: DIET & WEIGHT

Weekly semaglutide was linked to a 20% lower risk of heart attack, stroke, or death from heart disease in adults with overweight or obesity who already had cardiovascular disease but not diabetes, in a randomized trial of 17,604 people followed for more than three years. It was the first major trial to show that a medication aimed at body weight can also protect the heart.¹

Excess Weight Raises Blood Pressure and Fuels Inflammation

Carrying excess weight is one of the most common risk factors for heart disease, in part because it tends to raise blood pressure, worsen cholesterol, and fuel chronic inflammation—a slow, simmering irritation of blood vessels that encourages the buildup of artery-clogging plaque. Yet until this trial, no weight-focused medication had been shown to actually prevent the heart attacks and strokes that make obesity so consequential.

SELECT Randomly Assigned 17,604 Adults Aged 45 and Older

The SELECT trial enrolled 17,604 adults aged 45 and older across hundreds of clinical sites worldwide. All had overweight or obesity along with established cardiovascular disease—most had already survived a heart attack—but none had diabetes. Each was randomly assigned to a once-weekly injection of semaglutide, a medication that mimics a natural gut hormone which curbs appetite and helps control blood sugar, or to an identical-looking placebo; neither participants nor their doctors knew who received which. Over an average of about 40 months, independent committees tracked every heart attack, stroke, and cardiovascular death—the long follow-up and blinded design are what let the trial measure the medication’s true effect on these events.

Heart Events in 6.5% Versus 8.0% on Placebo

Serious heart events occurred in 6.5% of people taking semaglutide versus 8.0% of those on placebo—the 20% lower risk. Participants on the medication also lost about 9% of their body weight on average, compared with less than 1% on placebo. Notably, follow-up analyses suggest the heart protection was not fully explained by the amount of weight lost, hinting the medication may also act on blood vessels and inflammation directly.¹

16.6% Stopped Treatment Versus 8.2% on Placebo

Side effects—mostly digestive, such as nausea and diarrhea—led 16.6% of semaglutide users to stop treatment, versus 8.2% on placebo. The trial was funded by Novo Nordisk, the company that makes semaglutide, a standard arrangement in drug research that is still worth knowing about. And the results describe the population studied—adults with overweight or obesity who already had heart disease—not everyone whose weight is above the normal range.

Ten Trials in Nearly 68,000 People, 13% Fewer

Other research points the same way. A 2025 review pooling ten randomized trials of semaglutide and similar gut-hormone medications in nearly 68,000 people found about 13% fewer major heart events, with larger benefits at higher starting body weights.² A separate trial of 9,650 adults with type 2 diabetes and heart or kidney disease linked a daily semaglutide pill to 14% fewer such events over about four years.³

Key Takeaways

• In a randomized trial of 17,604 adults with overweight or obesity and existing heart disease, weekly semaglutide was linked to 20% fewer heart attacks, strokes, and cardiovascular deaths over about three and a half years.
• It was the first large trial to show a weight-focused medication preventing serious heart events, and the benefit did not appear to depend entirely on how much weight was lost.
• Digestive side effects were the main reason about one in six participants stopped the medication, and the trial was funded by its manufacturer.

References

1. 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
2. Kalayci A, Januzzi JL, Mitsunami M, et al. Clinical features modifying the cardiovascular benefits of GLP-1 receptor agonists: a systematic review and meta-analysis. European Heart Journal – Cardiovascular Pharmacotherapy. 2025;11(6):552–561. link.
3. 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.