Retatrutide
Reta · Triple-G
Triple-agonist (GLP-1/GIP/glucagon) investigational peptide; very potent weight loss.
Key takeaways
- Triple agonist (GLP-1/GIP/glucagon); investigational, not approved anywhere.
- Phase 2: 24.2% mean weight loss at 48 weeks on 12 mg weekly.
- ~6-day half-life supports once-weekly dosing; bioavailability is an estimate.
- GI effects dominate; a transient heart-rate rise peaked near 24 weeks in trials.
Overview
What it is
Retatrutide is an investigational once-weekly peptide that activates three receptors at once: GLP-1, GIP, and glucagon. Lilly is developing it for obesity and type 2 diabetes, with phase 3 trials underway and no approval anywhere.
Pharmacokinetics
The plotter models a roughly 6-day half-life with a peak around 1.7 days, supporting once-weekly subcutaneous dosing. The 80% bioavailability figure is an estimate; no robust published value exists, and anything sold today as retatrutide is grey-market material outside the trial supply chain.
What the evidence says
Phase 2 data (NEJM 2023) showed 24.2% mean weight loss at 48 weeks on the 12 mg dose, the largest yet reported for an incretin-class drug, with gastrointestinal effects leading the dropouts. A dose-related heart-rate increase peaked around 24 weeks and then declined. Nothing long-term exists yet.
Reported dosing protocols
Protocols reported in research literature and clinic/community use — informational context, not a dosing recommendation.
| Use case | Dose | Route | Frequency | Duration |
|---|---|---|---|---|
| Obesity (phase 2 trial) | Escalated to 4, 8, or 12 mg | SubQ | Once weekly | 48 weeks |
| Community (grey market) | 1–4 mg | SubQ | Once weekly | Varies |
Pharmacokinetic summary
- Model tier
- Advanced (t½ + Cmax + Tmax + F)
- Half-life
- 6.1 days
- Cmax
- 11495.37 nmol/L
- Tmax
- 1.7 days
- Bioavailability
- 80%
- Typical dose
- 1–12 mg
Frequently asked questions
Is retatrutide approved?
No. It remains in phase 3 development. Anything purchasable today is unregulated grey-market peptide, with no guarantee of identity, dose, or purity.
How is retatrutide different from tirzepatide?
Tirzepatide activates GLP-1 and GIP receptors; retatrutide adds glucagon receptor activity, which raises energy expenditure and hepatic fat oxidation. Phase 2 weight-loss numbers exceed tirzepatide's, but the drugs haven't been compared head to head.
What side effects showed up in trials?
Mostly gastrointestinal: nausea, vomiting, and diarrhea, dose-dependent and worst during escalation. A dose-related heart-rate increase appeared early, peaked around 24 weeks, then declined. Long-term safety is unknown.
References
- Cell Metabolism (retatrutide) — No good bioavailability source.
- Jastreboff et al., NEJM 2023 — retatrutide phase 2 — Randomized phase 2 trial: 24.2% mean weight loss at 48 weeks on 12 mg.
- Cell Metabolism 2022 — retatrutide phase 1 — Entry's PK source; early human PK and pharmacodynamics.
Related compounds
Semaglutide Injection (Ozempic/Wegovy)
Long-acting GLP-1 receptor agonist for type 2 diabetes and weight loss; weekly injection.
Semaglutide Oral (Rybelsus)
Oral semaglutide with very low bioavailability; taken fasting.
Tirzepatide (Mounjaro)
Dual GIP/GLP-1 agonist for weight loss and diabetes; weekly injection, strong efficacy.
Protocols featuring Retatrutide
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