In March 2024, the FDA approved Wegovy for cardiovascular event reduction in adults with obesity and established CVD — the first weight-management drug ever approved for a cardiovascular outcome. The basis was SELECT, the largest cardiovascular outcome trial of a GLP-1 receptor agonist in adults without diabetes.

The SELECT trial

SELECT (Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity) enrolled 17,604 adults with BMI ≥27 kg/m² and established cardiovascular disease, without diabetes. They received semaglutide 2.4 mg weekly or placebo, on top of standard CV care.

Endpoint	Semaglutide	Placebo	Effect
MACE (3-point composite)	6.5%	8.0%	20% relative risk reduction (HR 0.80, p<0.001)
CV death	2.5%	3.0%	HR 0.85
Non-fatal MI	2.7%	3.7%	HR 0.72
Non-fatal stroke	1.7%	1.9%	HR 0.93
Weight (52 weeks)	−9.4%	−0.9%	−8.5% difference

Median follow-up was 39.8 months. The MACE benefit emerged early (within 6 months) and persisted. Weight effect was modestly smaller than in STEP-1, consistent with the older, sicker SELECT cohort.

How SELECT changed clinical practice

The FDA label for Wegovy now includes CV event reduction in adults with BMI ≥27 and established CVD.
CMS announced (April 2026) that Medicare Part D plans may cover Wegovy under the SELECT-aligned indication, expanding access for Medicare beneficiaries who previously had no GLP-1 coverage for weight or CV benefit.
Many commercial plans have added Wegovy to formulary under prior authorization criteria mirroring SELECT enrollment.

What "established CVD" means here

SELECT enrolled patients with any of the following: prior myocardial infarction, prior ischemic or hemorrhagic stroke, or symptomatic peripheral arterial disease. Patients with diabetes were excluded (a separate pathway exists for T2D + CVD via SUSTAIN-6).

Mechanism beyond weight loss

The CV benefit in SELECT outpaces what would be expected from weight loss alone in similar trials. Proposed mechanisms include direct GLP-1 receptor effects in vascular endothelium and myocardium, reduced systemic inflammation, improved insulin sensitivity, and blood pressure reduction. The clinical implication is that the CV benefit is not solely a "lose weight, lower CV risk" story — there is direct pharmacologic benefit.

What we don't yet know

Primary prevention in obesity without established CVD: Not studied in SELECT. The 2026 STEP-HFpEF, STEP-Kidney, and similar trials extend the benefit profile but do not address primary CV prevention in lower-risk adults with obesity.
Tirzepatide CV outcomes: SURPASS-CVOT reads out 2026; if positive on MACE, an FDA CV indication for Zepbound is likely to follow.
Long-term effects beyond 5 years: No GLP-1 CV outcome trial has yet extended past 5-year follow-up in obesity populations without diabetes.

Clinical takeaways

For adults with obesity and established CVD, semaglutide 2.4 mg is now a guideline-aligned CV risk-reduction therapy.
The MACE benefit appears within months and is sustained.
Coverage barriers are easing. Discuss with the prescriber whether Wegovy through insurance is now accessible.
Compounded semaglutide has the same active ingredient, but does not have FDA-approved labeling for CV risk reduction, and most CV physicians prefer the FDA-approved branded product when accessible.