Research
Hormonal
GLP-1 receptor agonists (semaglutide, tirzepatide) provide significant cardiovascular benefits, including a 20% reduction in major adverse cardiovascular events (MACE) in patients with obesity and pre-existing cardiovascular disease but without diabetes.
If you have obesity and existing heart disease, even without diabetes, taking semaglutide (2.4 mg weekly) can significantly lower your risk of heart attack, stroke, or cardiovascular death by about 20%. This benefit appears to come from the drug's direct effects on the body, not just from losing weight.
StrongSupportsVERY_HIGH confidence
this randomized placebo-controlled study of more than 17,000 participants with pre-existing cardiovascular disease and overweight/obesity but without type 2 diabetes demonstrated a 20% reduction in a composite primary outcome of cardiovascular death, non-fatal myocardial infarction and stroke in those treated with semaglutide 2.4 mg weekly over a mean of 3.3 years (HR 0.80; 95% ci 0.72 to 0.90; p < 0.001) [25].
Why this rating
Based on the SELECT trial, a large, randomized, placebo-controlled outcome trial.
Source
Medical management of obesity: unlocking the potential
Angie S. Xiang et al. · Climacteric · 2025
DOI 10.1080/13697137.2025.2455177
narrative_review
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- New-generation incretin-based obesity medications (semaglutide 2.4 mg weekly and tirzepatide 5-15 mg weekly) achieve mean weight loss exceeding 10-15%, which is two- to three-fold greater than previous obesity medications.Strong
- Tirzepatide (5, 10, and 15 mg weekly) improves metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis in patients with biopsy-confirmed MASH and stage F2 or F3 fibrosis.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
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