Research
Hormonal
Semaglutide 2.4 mg once weekly significantly reduces major adverse cardiovascular events (MACE) and all-cause mortality in individuals with obesity and established atherosclerotic cardiovascular disease (ASCVD), regardless of diabetes status.
If you have obesity and established heart disease, semaglutide 2.4 mg once weekly is a preferred first-line treatment to significantly reduce your risk of heart attacks, strokes, and death, even if you do not have diabetes. This should be combined with lifestyle therapy.
StrongSupportsVERY_HIGH confidence
In the SELECT trial, semaglutide 2.4 mg once weekly (OW) reduced MACE (CV death, nonfatal myocardial infarction (MI), stroke) by 20% (HR 0.80; 95% CI 0.72–0.90) and all-cause mortality by 19% in subjects with obesity and established ASCVD but without diabetes [4].
Why this rating
Based on a large, phase III randomized controlled trial (SELECT) with prespecified primary endpoints.
Source
Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan
Dario Tuccinardi et al. · Journal of Endocrinological Investigation · 2025
DOI 10.1007/s40618-025-02700-7
narrative_reviewCited 9×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Semaglutide 2.4 mg once weekly is the preferred first-line anti-obesity medication for individuals with obesity and chronic kidney disease (CKD), including non-diabetic populations, due to significant reductions in renal endpoint progression.Strong
- Tirzepatide 15 mg once weekly is preferred for individuals with obesity and prediabetes when greater weight loss is needed, achieving a 94% risk reduction in diabetes progression over 72 weeks.Strong
- Tirzepatide 15 mg once weekly is preferred for individuals with obesity and heart failure with preserved ejection fraction (HFpEF) to improve symptoms and functional capacity, irrespective of glycemic status or weight loss magnitude.Good
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →