CATEGORY: DIET & WEIGHT
Weekly semaglutide lowered the risk of heart attack, stroke or death from heart disease by 20% in adults with overweight or obesity who already had cardiovascular disease but not diabetes. The trial randomized 17,604 people and followed them for more than three years.1 No medication aimed at body weight had ever been shown to do that.
Why a Weight Drug Might Touch the Heart at All
Excess weight sits among the most common risk factors for heart disease. It tends to push blood pressure up, worsen cholesterol, and feed chronic inflammation, a slow-simmering irritation of blood vessels that encourages artery-clogging plaque to build. The reasoning was easy enough. What did not exist was evidence that a drug aimed at body weight actually prevented the heart attacks and strokes that make obesity so consequential.
40 Months of Logged Heart Attacks and Strokes
SELECT enrolled 17,604 adults aged 45 and older at hundreds of clinical sites worldwide. All carried overweight or obesity alongside established cardiovascular disease, and most had already survived a heart attack. None had diabetes. A once-weekly injection of semaglutide went to half of them and an identical-looking placebo to the rest, with the allocation hidden from participants and their doctors alike. Semaglutide mimics a natural gut hormone that curbs appetite and helps control blood sugar. For an average of about 40 months, independent committees logged every heart attack, stroke and cardiovascular death, and that long blinded stretch is what let the trial measure a real effect rather than an impression.
6.5% Versus 8.0%, and Weight Loss Explains Only Part of It
Serious heart events struck 6.5% of the semaglutide group and 8.0% of the placebo group. That is the 20%. People on the medication lost about 9% of their body weight on average, against less than 1% on placebo. Follow-up analyses suggest the heart protection was not fully explained by how much weight came off, hinting that the drug acts on blood vessels and inflammation directly as well.1
One in Six Stopped Taking It
Side effects, mostly digestive ones such as nausea and diarrhea, led 16.6% of semaglutide users to quit treatment, versus 8.2% on placebo. Novo Nordisk, the maker of semaglutide, funded the trial. The findings describe the people studied, adults with overweight or obesity and existing cardiovascular disease, rather than everyone whose weight sits above the normal range. Related drugs line up behind the result. 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 Among 9,650 adults who had type 2 diabetes plus heart or kidney disease, a daily semaglutide pill was linked to 14% fewer such events over about four years.3
Key Takeaways
- Weekly semaglutide lowered heart attacks, strokes and cardiovascular deaths by 20% over roughly 40 months in adults carrying excess weight alongside existing heart disease.
- This was the first large trial in which a weight-focused medication prevented serious heart events, and the benefit did not appear to hinge entirely on how much weight was lost.
- Digestive side effects drove roughly one in six participants off the medication, and the manufacturer paid for the trial.
References
- 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
- 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.
- 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.