Fat loss
Retatrutide
Investigational triple-hormone-receptor agonist with the largest weight-loss effect of any GLP-1-class compound tested so far. Not FDA-approved.
Investigational (Phase 3) Fat loss
- Full name
- Retatrutide (triple GIP/GLP-1/glucagon receptor agonist)
- Also known as
- LY3437943, Triple-G agonist
- Regulatory status
- Investigational — in Phase 3 clinical trials as of this writing, not yet FDA-approved for any indication. Available through research-chemical/grey-market channels despite lacking approval, which carries significant additional risk versus using a regulated, approved drug.
Origin
Developed by Eli Lilly. A single synthetic peptide engineered to hit three receptors at once: GLP-1, GIP, and glucagon. The first 'triple agonist' in this class to reach late-stage trials.
Mechanism
Combines GLP-1 and GIP receptor activity (as in tirzepatide) with glucagon receptor agonism, which raises energy expenditure and drives lipolysis in the liver. That stacks a metabolic-rate effect on top of the appetite suppression the other GLP-1-class drugs already provide.
Research summary
Evidence
A Phase 2 trial in the New England Journal of Medicine reported average weight loss around 24% of body weight at the highest dose (12 mg/week) at 48 weeks, the largest effect size reported for this class at time of publication. Weight loss was still trending down, not plateaued, at trial's end, suggesting more loss with continued treatment. Phase 3 trials are underway to confirm long-term efficacy and safety at scale; longer-term glucagon-receptor effects are still being worked out.
Evidence tier: Investigational (Phase 3) — see the methodology note for how this is assessed.
Citations
- Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial — Jastreboff et al. 2023
- The power of three: Retatrutide's role in modern obesity and diabetes therapy — Abdul-Rahman et al. 2024
Reported benefits
- Largest average weight-loss effect reported for any GLP-1-class compound in trials to date
- Added metabolic-rate/energy-expenditure component beyond pure appetite suppression, due to glucagon receptor activity
- Trial data suggests effect had not plateaued by 48 weeks, unlike some comparator trials
Dosing protocols reported in the literature & community
These are protocols reported by compounding pharmacies, published trials, or self-experimentation communities — not a prescription. Start low, especially for anything new.
| Route | Reported protocol |
|---|---|
| Subcutaneous injection, once weekly (as studied in trials) | Phase 2 trial dosing escalated up to 12 mg/week; because this drug is not yet approved, there is no standardized prescribing protocol, and self-sourced dosing is based on extrapolating from trial data rather than an established, regulated titration schedule. |
Side effects
- GI side effects similar to but potentially more pronounced than semaglutide/tirzepatide given the added glucagon receptor activity, including nausea, diarrhea and reduced appetite
- Increased heart rate has been observed in trials, thought related to glucagon receptor activation — a distinguishing safety signal versus the dual/single agonists
- Long-term safety data does not yet exist at the scale available for semaglutide or tirzepatide
Safety notes
Community & reddit notes (anecdotal — not clinical evidence)
Big buzz in weight-loss and longevity circles as the 'next generation' GLP-1 drug on the strength of its trial results. But access is entirely grey-market research-chemical sourcing since it isn't FDA-approved, a meaningfully different risk than prescribed semaglutide or tirzepatide. Weigh that against just waiting for approval or using what's already approved.
Related peptides
Used in stacks
Community combinations that include Retatrutide — see each stack page for the combination-specific rationale and evidence.
Mixing compatibility
Pulled from a community-charted mixing-compatibility reference (anecdotal, clinic-use, and community-reported signals) — not a safety guarantee. Verify independently before combining anything.