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How GLP-1s Work

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The gut hormone that ate the world

GLP-1 (glucagon-like peptide-1) is released by your gut after you eat. It tells your pancreas to release insulin, slows gastric emptying, and signals to your brain that you're full. Semaglutide (Ozempic/Wegovy), tirzepatide (Mounjaro/Zepbound), and retatrutide are engineered long-acting mimics.

3 sites gut, pancreas, brain
Fact

Weight loss: ~15% at one year

In the STEP 1 trial, once-weekly semaglutide 2.4 mg drove mean body-weight loss of 14.9% at 68 weeks vs. 2.4% on placebo. Tirzepatide's SURMOUNT-1 pushed that to 20.9% at the 15 mg dose — the first non-surgical weight-loss effect in that range.

21% tirzepatide SURMOUNT-1, 72 wks
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Three levers at once

Tap each mechanism to see how GLP-1s reshape appetite and glucose.

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Insight

The cardiovascular bonus

The SELECT trial (17,604 patients with heart disease + obesity, no diabetes) showed semaglutide reduced major cardiovascular events by 20% over 40 months. This is the first obesity drug with a proven cardiovascular benefit — and one reason cardiologists are now prescribing it, not just endocrinologists.

20% MACE reduction, SELECT
Fact

Single → dual → triple agonists

Semaglutide hits one receptor (GLP-1). Tirzepatide hits two (GLP-1 + GIP) — and produces about a third more weight loss at the same tolerability. Retatrutide adds a third receptor (glucagon) and pushed phase-2 weight loss to 24 % at 48 weeks (Jastreboff 2023, NEJM). The trend is clear: more receptors hit simultaneously = more aggressive metabolic remodelling. Triple agonists are expected to land in 2026–2027 and will likely become the standard of care for severe obesity.

1→2→3 receptor classes
Takeaway

Key Takeaway

GLP-1 agonists work on three axes simultaneously — pancreas, stomach, and brain — and now have proven cardiovascular benefit beyond weight loss. The drug class is also evolving fast: dual (tirzepatide) and triple (retatrutide) agonists are pushing weight-loss effects toward 25 %+, with broader metabolic benefit. That combination is why they've become the fastest-growing drug class in modern medicine.

References

  1. STEP 1 — semaglutide 2.4 mg once weekly for obesityWilding et al., 2021
  2. SURMOUNT-1 — tirzepatide once weekly for obesityJastreboff et al., 2022
  3. SELECT — semaglutide and cardiovascular outcomes in obesity without diabetesLincoff et al., 2023
  4. Retatrutide phase-2 — triple agonist for obesityJastreboff et al., 2023

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GLP-1 Longevity Signals