Retatrutide (investigational)

The most-watched pipeline molecule — a "triple agonist" that produced about 24% average weight loss in phase 2, the largest ever reported for a medication. Not yet available; beware of anyone selling it.

What retatrutide is Retatrutide activates three receptors — GLP-1, GIP, and glucagon — adding an energy-expenditure (“burn more”) mechanism on top of the appetite-suppression (“eat less”) mechanisms of current drugs. ## The evidence so far - Phase 2 (NEJM, 2023): average weight loss of 24.2% at 48 weeks on the highest dose — and the curve had not plateaued. Essentially all participants on higher doses lost ≥5%. - Phase 3 (TRIUMPH program): large trials in obesity, sleep apnea, knee osteoarthritis, and related conditions are underway/reading out. Until full phase 3 data and FDA review, effectiveness and safety claims rest on phase 2. Notable signals to watch: heart-rate increases were observed at higher doses, and the glucagon mechanism affects liver fat in interesting ways — phase 3 will clarify both. ## The scam warning Because retatrutide is famous and unavailable, it is the single most counterfeited “GLP-1” online. There is no legitimate way to buy retatrutide today. It cannot legally be compounded (it is not an FDA-approved drug, so pharmacies have no approved reference to compound from). Anything sold as “retatrutide” on peptide or “research chemical” sites is unregulated powder of unknown identity, purity, and dose. If you want triple-agonist results in the future, the safe play is straightforward: take an approved GLP-1 now if indicated, and switch later if retatrutide earns approval. ## Also in the pipeline - Oral semaglutide 25 mg for obesity (regulatory review) — see oral semaglutide - CagriSema (cagrilintide + semaglutide): ≈20%+ weight loss in phase 3 - Orforglipron: a daily non-peptide pill, ≈12% weight loss in phase 3 — no injections, no fasting ritual, easier manufacturing