Does semaglutide reduce cardiovascular events in adults with obesity but without diabetes?

Bottom line: Yes, but only in a specific group: in adults with obesity or overweight, established cardiovascular disease and no diabetes, semaglutide 2.4 mg lowered cardiovascular events in one large randomized trial. Certainty is moderate by my own reading, because most of the evidence comes from that single trial [1].

What the studies found:
- SELECT trial (randomized, double-blind, placebo-controlled): 17,604 patients aged 45 or older with BMI of 27 or more, preexisting cardiovascular disease and no diabetes. The primary composite (cardiovascular death, nonfatal heart attack or nonfatal stroke) occurred in 6.5% on semaglutide versus 8.0% on placebo, over a mean follow-up of 39.8 months [1]. A later report describes this as a 20% reduction [2].
- Weight effects in SELECT: weight fell 10.2% at 208 weeks on semaglutide versus 1.5% on placebo, and the loss was sustained for up to 4 years [2].
- Pooled analyses across populations: a meta-analysis of 8 semaglutide trials (39,204 patients) found MACE HR 0.82 (95% CI 0.77-0.87) [3]. Another, of 35 trials, found RR 0.84 (0.77-0.92) [4]. These pool people with and without diabetes, so they are indirect for your question.
- Heart failure: in people without baseline heart failure, semaglutide's risk ratio was 0.69 (0.55-0.88) [5]. This pools diabetes and/or obesity trials.

Where it is uncertain: The studies found do not report a separate pooled estimate for non-diabetic obesity. The direct evidence is one trial in people with existing cardiovascular disease. Discontinuations rose as BMI class fell, and weight regain after stopping GLP-1 drugs is documented [6][2]. Several of the pooled reviews are recent and I could not check their risk-of-bias ratings from the excerpts.

What this does and does not support: The evidence supports a cardiovascular benefit of semaglutide 2.4 mg in adults with obesity and established cardiovascular disease but no diabetes. It does not show benefit for primary prevention in people without cardiovascular disease.

This is not medical advice; talk to your doctor about your situation.

Studies cited
1. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. Randomized trial · The New England journal of medicine · 2023 · PubMed
2. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Randomized trial · Nature medicine · 2024 · PubMed
3. Effects of semaglutide on mortality, cardiovascular, and kidney outcomes across the cardio-kidney-metabolic continuum: a systematic review and meta-analysis. Meta-analysis · Cardiovascular diabetology · 2026 · PubMed
4. Semaglutide Beyond Diabetes and Obesity: Systematic Review and Meta-Analysis of Multisystem Therapeutic Benefits. Meta-analysis · Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2026 · PubMed
5. Glucagon-like peptide-1 receptor agonists for prevention of heart failure events in type 2 diabetes and/or obesity. Meta-analysis · ESC heart failure · 2026 · PubMed
6. Weight regain following discontinuation of glucagon-like peptide-1 receptor agonists in adults who are overweight or obese: a systematic review and meta-analysis. Meta-analysis · PeerJ · 2026 · PubMed

Searched Europe PMC: (semaglutide OR "GLP-1 receptor agonist") AND (obesity OR overweight) AND ("cardiovascular events" OR "major adverse cardiovascular events") · 12 found, 6 cited · also looked for: SELECT

This summarizes published research. It is not medical advice: talk to a clinician about your own situation.

Also discussed here:
- Study: 54% of adults under 45 with type 2 diabetes reached remission in six months