Retatrutide
Next-gen triple agonist from Eli Lilly hitting GLP-1, GIP, and glucagon receptors. Phase 2 showed 24.2% weight loss at 48 weeks — highest of any incretin therapy. At low doses, optimizes metabolism without major weight loss.
Key Facts
- ClassificationRetatrutide (LY3437943) is a triple GIP/GLP-1/glucagon agonist.
- Primary BenefitsFat Loss (10/10) · Brain & Cognition (5/10) · Longevity (5/10)
- AdministrationInjection
- Typical DoseFor health optimization: 2 mg per week (start at 1 mg for the first 4 weeks). For weight loss: gradually increase from 1 to 4 to 8 to 12 mg over months. Its long half-life (4-7 days) means you only inject once a week.
- Evidence StrengthModerate — 21 peer-reviewed studies referenced · Community sentiment 9/10
- Stacks Well With5-Amino-1MQ, MOTS-c, SS-31, NAD+
- Legal StatusPhase 2/3 Clinical Trials · not prescribable in US · WADA prohibited
Quick Facts
- From price
- $95
- Type
- peptide
- Administration
- Injection
- Evidence
- moderate
- Studies referenced
- 21
- Community sentiment
- 9/10
- Stacks with
- 5 peptides
- Regulatory
- Phase 2/3 Clinical Trials
Top benefits
Week 1–2
Appetite suppression with possible GI adjustment. Nausea during titration similar to GLP-1 agonists. Start low and titrate slowly over weeks.
Week 3–6
Accelerated weight loss exceeding dual-agonist compounds. Increased thermogenesis (feeling warmer). Improved energy from glucagon-mediated fat oxidation.
Week 8+
Potentially the most aggressive weight loss of any incretin agonist (20-24% body weight). Significant metabolic improvement. Hepatic fat reduction.
Common Side Effects
Scientific Overview
Retatrutide (LY3437943) is a triple GIP/GLP-1/glucagon agonist. The glucagon component adds thermogenic and lipolytic effects. Phase 2 showed 24.2% weight reduction at 48 weeks — the most potent weight loss in any obesity pharmacotherapy trial. Produces synergistic effects on energy expenditure and hepatic lipid metabolism.
Dosing
For health optimization: 2 mg per week (start at 1 mg for the first 4 weeks). For weight loss: gradually increase from 1 to 4 to 8 to 12 mg over months. Its long half-life (4-7 days) means you only inject once a week.
Reconstitution, storage, injection sites & timing
Benefit Profile
| Vendor | Variant | Price | |
|---|---|---|---|
| Limitless Biotech | 3mg | $99.99 | Code: PSTACK10Buy |
| Skye Peptides | 3mg | $94.99BEST | |
| Peptide Sciences ✕ Announced voluntary shutdown — stock availability may be limited or unavailable. Pricing data may be outdated. | 3mg | $109.00 | Out of stock |
Stacks Well With
5-Amino-1MQ
Small molecule blocking NNMT, an enzyme that slows metabolism. Increases NAD+ production and energy expenditure. Promotes fat loss and may fix metabolic issues.
MOTS-c
Mitochondrial DNA-encoded peptide that activates AMPK, improving insulin sensitivity, fat burning, and mimicking exercise at the cellular level. Stacks well with SS-31 and NAD+.
SS-31 (Elamipretide)
Engineered to target inner mitochondrial membrane via cardiolipin binding. Stabilizes cristae, improves ATP production, and reduces oxidative stress. FDA-approved for Barth syndrome (as Forzinity) — the first FDA-approved mitochondria-targeted therapy.
NAD+ (Nicotinamide Adenine Dinucleotide)
Critical molecule for cellular energy and DNA repair. Levels may drop ~50% by middle age. Activates sirtuin longevity genes and powers PARP DNA repair enzymes. Injectable form bypasses oral absorption issues.
BPC-157
A healing compound from human gastric juice. The most extensively studied repair peptide in animal models, with strong preclinical data for tissue repair, gut restoration, and anti-inflammatory effects. Human clinical data remains limited.
Compare
Semaglutide and Retatrutide represent two different generations of incretin-based weight loss therapies. Semaglutide is a GLP-1 receptor agonist with extensive clinical data and FDA approval, while Retatrutide is a novel triple agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. The addition of glucagon receptor activation distinguishes Retatrutide from all currently approved therapies and introduces a thermogenic component that may drive greater fat loss -- but it remains in clinical trials.
Tirzepatide vs Retatrutide: Dual vs Triple AgonistTirzepatide and Retatrutide are both multi-receptor agonists developed by Eli Lilly, but they target different numbers of receptors. Tirzepatide is a dual GIP/GLP-1 agonist with FDA approval and robust phase III data, while Retatrutide adds a third target -- the glucagon receptor -- creating the first triple agonist in clinical development for obesity. This comparison examines whether the additional glucagon receptor activation translates to meaningfully better outcomes.
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