What if the next major breakthrough in weight loss and metabolic health could far outperform today’s most popular injectable, with fewer plateaus and broader benefits? That’s exactly what's brewing with Retatrutide. It’s a novel triple-hormone peptide showing transformative results in clinical trials, and it may well eclipse Ozempic (semaglutide)—even though semaglutide already changed the game.
In the New England Journal of Medicine, Phase 2 Trial, a landmark trial involving 338 adults with obesity (no diabetes) tested weekly doses of Retatrutide (1–12 mg). At 48 weeks, the highest dose group lost an average of 24.2% of body weight—with weight loss still trending downward with no plateau reached (New England Journal of Medicine).
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Nearly 100% of participants on 8–12 mg lost at least 5% of weight; 83% lost 15% or more (New England Journal of Medicine).
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The treatment also delivered big wins in reducing HbA1c, triglycerides (~40%), LDL cholesterol (~22%), and blood pressure (Healio).
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Side effects were generally mild gastrointestinal issues during dose escalation, and heart rate increases peaked mid-study but declined later (New England Journal of Medicine).
Semaglutide (Ozempic) — STEP Trials, Phase III Data
In one of the largest randomized trials (N≈1,960), weekly semaglutide led to ~14.9% weight loss over 68 weeks compared to ~2.4% in placebo.
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Effective—but weight loss tends to plateau, and most patients regain weight if the treatment is stopped.
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Benefits include strong glucose control and reduced heart risk—but limited impact on lipids and liver fat.
Why Retatrutide May Be the Long-Term Winner
| Feature | Ozempic (Semaglutide) | Retatrutide (Triple‑Agonist Peptide) |
|---|---|---|
| Peak Weight Loss | ~15% over ~1.3 years | ~24% at 48 weeks, with no plateau yet |
| Proportion ≥15% Weight Loss | ~30–50% of participants | ~83% at highest doses |
| Metabolic Benefits | Improved blood sugar, heart risk | Also reduces liver fat, lipids, BP, insulin resistance |
| Long-Term Sustainability | Plateaus, weight gain possible after discontinuation | Retatrutide still showed declining weight at week 48 |
| Action Mechanism | Activates GLP‑1 receptor only | Activates GLP‑1, GIP, and glucagon receptors |
Retatrutide’s ability to hit multiple hormone pathways may offer more sustained effects on appetite suppression, fat burning, and metabolic health simultaneously—something semaglutide, with its single-receptor approach, doesn’t match.
While semaglutide (Ozempic) is already established and FDA-approved, Retatrutide is setting unprecedented benchmarks in weight loss and metabolic control. Its phase 2 data show nearly twice the weight loss, superior lipid and glycemic benefits, and little sign of plateauing. That said, it remains investigational and full approval hinges on upcoming Phase 3 TRIUMPH trials.
Jastreboff et al. Phase 2 Trial of Triple‑Hormone‑Receptor Agonist Retatrutide for Obesity. New England Journal of Medicine. 2023; up to 24.2% weight loss at 48 weeks (Reddit, Healio, clinicalbiostats.com, NewBody Rx, reuters.com, New England Journal of Medicine, Reddit, BioSpace, Reddit)
Semaglutide Obesity Phase III Trial (STEP): once‑weekly semaglutide led to ~14.9% weight reduction at week 68 vs placebo (~2.4%) (Wikipedia)