Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

The SELECT trial, a randomized, placebo-controlled, event-driven superiority study evaluated whether once-weekly semaglutide 2.4 mg reduces major adverse cardiovascular events in 17,604 patients aged ≥45 with established cardiovascular disease, BMI ≥27, and no diabetes. Over a mean follow-up of 39.8 months, semaglutide significantly lowered the composite endpoint (CV death, nonfatal MI, or nonfatal stroke) from 8.0% to 6.5% (HR 0.80; P < 0.001). Weight loss averaged 9.4% vs. 0.88%, with improvements in blood pressure, lipids, inflammation (↓hsCRP 38%), glycemic control, and waist circumference. The drug reduced nonfatal MI (HR 0.72), coronary revascularization (HR 0.77), and nephropathy (HR 0.78). Adverse event discontinuation was higher with semaglutide (16.6% vs. 8.2%), driven by gastrointestinal effects. The trial did not include patients without established CV disease, limiting primary-prevention implications. Nevertheless, SELECT confirmed semaglutide’s cardioprotective benefit in high-risk obese patients without diabetes—mirroring prior GLP-1 data in diabetics, and opening pathways for expanded use in obesity management.

The SELECT trial, a randomized, placebo-controlled, event-driven superiority study evaluated whether once-weekly semaglutide 2.4 mg reduces major adverse cardiovascular events in 17,604 patients aged ≥45 with established cardiovascular disease, BMI ≥27, and no diabetes. Over a mean follow-up of 39.8 months, semaglutide significantly lowered the composite endpoint (CV death, nonfatal MI, or nonfatal stroke) from 8.0% to 6.5% (HR 0.80; P < 0.001). Weight loss averaged 9.4% vs. 0.88%, with improvements in blood pressure, lipids, inflammation (↓hsCRP 38%), glycemic control, and waist circumference. The drug reduced nonfatal MI (HR 0.72), coronary revascularization (HR 0.77), and nephropathy (HR 0.78). Adverse event discontinuation was higher with semaglutide (16.6% vs. 8.2%), driven by gastrointestinal effects. The trial did not include patients without established CV disease, limiting primary-prevention implications. Nevertheless, SELECT confirmed semaglutide’s cardioprotective benefit in high-risk obese patients without diabetes—mirroring prior GLP-1 data in diabetics, and opening pathways for expanded use in obesity management.