SELECT TRIAL: GLP-1S CUT HEART ATTACKS 20% — EVEN WITHOUT DIABETES

🎯 The Bottom Line

The SELECT trial enrolled 17,604 patients with obesity and established cardiovascular disease — but without diabetes. Semaglutide 2.4mg reduced heart attacks, strokes, and cardiovascular death by 20%. Benefits appeared within 3 months. This led to FDA approval for cardiovascular risk reduction — a first for any weight loss drug.

WHY THIS TRIAL CHANGED EVERYTHING

Before SELECT, GLP-1 medications were "diabetes drugs that also help with weight loss." After SELECT, they're recognized as cardiovascular protection drugs that happen to also treat diabetes and obesity.

This isn't semantics. It fundamentally changes who should consider these medications and why. If you have obesity and heart disease risk factors, GLP-1s aren't just about the scale — they may help you live longer.

20%
Reduction in major adverse cardiovascular events (heart attacks, strokes, CV death)

THE NUMBERS

17,604
Patients enrolled
39.8
Months average follow-up
3
Months to see benefits
0%
Patients with diabetes (exclusion criteria)

SELECT specifically excluded diabetics to prove that semaglutide's cardiovascular benefits aren't just about blood sugar control. Everyone in the trial had obesity (BMI ≥27) plus established cardiovascular disease — meaning prior heart attack, stroke, or symptomatic peripheral artery disease.

The 20% reduction in MACE (major adverse cardiovascular events) breaks down to fewer heart attacks, fewer strokes, and fewer cardiovascular deaths. All three components showed benefit.

BENEFITS APPEARED FAST

One of SELECT's most striking findings: the survival curves separated within 3 months. That's remarkably fast for a cardiovascular outcome trial.

Month 1-2
Titration phase. Minimal weight loss expected. GLP-1 receptors activated throughout body.
Month 3
Cardiovascular benefit curves begin to separate. Effect independent of amount of weight lost.
Month 6-12
Benefits continue to accumulate. Weight loss typically reaches 10-15%.
Month 12+
Sustained cardiovascular protection continues throughout treatment.

This rapid onset suggests GLP-1s protect the heart through mechanisms beyond weight loss — likely including direct effects on blood vessel function, inflammation, and cardiac metabolism.

HOW GLP-1S PROTECT THE HEART

The cardiovascular benefits are probably multifactorial:

  • Reduced inflammation: SELECT showed significant drops in CRP (C-reactive protein), a marker of systemic inflammation linked to heart disease
  • Improved blood vessel function: GLP-1 receptors exist in blood vessels; activation appears to improve endothelial function
  • Blood pressure reduction: ~5-6 mmHg systolic reduction on average
  • Weight loss: Reduces mechanical stress on the heart and improves metabolic health
  • Direct cardiac effects: GLP-1 receptors in heart muscle may provide direct protection

Importantly, the cardiovascular benefit in SELECT was greater than what you'd predict from weight loss alone. Something beyond the scale is happening.

FDA APPROVAL FOR HEART PROTECTION

Based on SELECT, the FDA approved Wegovy (semaglutide 2.4mg) in March 2024 for cardiovascular risk reduction in adults with obesity and established cardiovascular disease — without requiring diabetes.

🏥 What This Means for Insurance

The cardiovascular indication gives doctors a stronger case for coverage. Instead of just "weight loss" (often excluded), the prescription is for "cardiovascular risk reduction" (harder to deny). If you have obesity plus heart disease history, this may help with insurance appeals.

WHO SHOULD CONSIDER THIS

Strong Candidates Based on SELECT

  • BMI ≥27 (overweight) or ≥30 (obese)
  • History of heart attack, stroke, or peripheral artery disease
  • With or without diabetes

Likely to Benefit (Extrapolating From Data)

  • Obesity with multiple cardiovascular risk factors (even without prior events)
  • Strong family history of heart disease
  • Obesity with elevated inflammatory markers

TALK TO A PROVIDER

If you have obesity and cardiovascular risk factors, GLP-1s may offer more than weight loss.

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📚 Sources

[1] Lincoff AM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes." NEJM. 2023.

[2] FDA Approval Letter. Wegovy Cardiovascular Indication. March 2024.

[3] Verma S, et al. "Cardiovascular Effects of GLP-1 Receptor Agonists." Circulation. 2024.