WEIGHT LOSS · Injectable
Retatrutide.
Triple agonist: GLP-1 + GIP + glucagon receptor
How it works
Class & mechanism.
Class
Triple GLP-1/GIP/Glucagon Receptor Agonist
Mechanism
Retatrutide (LY3437943) is a synthetic peptide that simultaneously activates three hormone receptors — GLP-1, GIP, and glucagon (GCG) — with highest potency at the GIP receptor (EC50: 0.064 nM). GLP-1 and GIP receptor agonism suppresses appetite, slows gastric emptying, and enhances glucose-dependent insulin secretion, while the addition of glucagon receptor activation uniquely increases resting energy expenditure through thermogenesis and directly stimulates hepatic fatty acid oxidation and lipolysis. This triple-receptor mechanism produces a synergistic effect on caloric intake reduction, fat mobilization, and metabolic rate that exceeds the efficacy of dual or single agonists.
Did you know
In Phase 3 TRIUMPH-4 (Dec 2025), retatrutide's average weight loss of 28.7% at 68 weeks matches the efficacy of Roux-en-Y gastric bypass surgery — making it the first drug to approach bariatric-surgery-level results. Uniquely, the glucagon receptor component prevents the metabolic slowdown typical of dieting by actively increasing calorie burning at rest.
Benefits
What it does.
Dramatic weight reduction — up to 28.7% body weight loss at 68 weeks in Phase 3 TRIUMPH-4
Increased resting energy expenditure via glucagon receptor activation (fat burning at rest)
Liver fat reduction up to 86% at 12 mg dose — 93% of patients achieving normal liver fat levels
Improved glycemic control with HbA1c reductions of 1.7–2.0% and 82% achieving HbA1c ≤6.5%
Significant relief from knee osteoarthritis pain and improvements in physical function
Favorable cardiovascular risk factor improvements: reduced triglycerides, blood pressure, non-HDL cholesterol
The science
Peer-reviewed findings.
Research supporting this compound's mechanisms and safety profile.
Phase 2 trial (NEJM 2023): Participants on 12 mg retatrutide lost 24.2% of body weight at 48 weeks — 100% achieved ≥5% loss, 93% achieved ≥10%, 83% achieved ≥15%
SOURCE · New England Journal of Medicine, Phase 2 RCT, 2023
TRIUMPH-4 Phase 3 trial (December 2025): Average weight loss of 28.7% (-32.3 kg / 71.2 lbs) at 68 weeks on 12 mg dose, with 14% of patients achieving complete resolution of knee pain
SOURCE · Eli Lilly TRIUMPH-4 Phase 3, December 2025
Nature Medicine Phase 2a liver sub-study (2024): 12 mg dose reduced liver fat by 86% at 48 weeks; two-to-threefold increase in beta-hydroxybutyrate indicating direct hepatic fatty acid oxidation from glucagon activity
SOURCE · Nature Medicine, Harrison et al., 2024
TRANSCEND-T2D-1 Phase 3 (March 2026): Met all primary and secondary endpoints in T2D patients — HbA1c reduced by up to 2.0% and body weight by up to 16.8% at 40 weeks vs. -0.8% and -2.5% for placebo
SOURCE · Eli Lilly TRANSCEND-T2D-1, Phase 3, 2026
Protocol
How to use it.
Dosing
Once-weekly subcutaneous injection with stepwise titration: 2 mg (weeks 1–4) → 4 mg (weeks 5–8) → 8 mg (weeks 9–12) → 12 mg (week 13+). Maximum studied dose: 12 mg/week. Titration minimizes gastrointestinal side effects during dose escalation.
Cycle
Ongoing treatment required for sustained benefit — weight regain expected on discontinuation. Phase 3 trials run 40–68 weeks; long-term maintenance studies underway (TRIUMPH-Outcomes, 116-week follow-up). Currently investigational; FDA approval anticipated late 2026 or early 2027.
Contraindications
When to skip it.
Contraindicated with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN-2). Not for use in patients with chronic or acute pancreatitis. Common adverse events: nausea (16–27%), diarrhea (19–26%), vomiting (15–18%) — mostly during dose escalation. Mild dysesthesia reported in 2–5% of patients, generally resolves during treatment.
Always cleared with your concierge before protocol start.
Pricing
What it costs.
Indicative range for Retatrutide, sourced from vetted US and EU dispensing suppliers. Concierge confirms the exact figure once your match is locked.
Indicative range (USD)
Sourced through vetted dispensing partners in the United States and European Union. Concierge confirms the exact figure once your match is locked.
- 0199% purity verified, third-party tested
- 02Includes vial and reconstitution guidance
- 03Concierge supplier match included with every protocol
See Retatrutide pricing — and your supplier match.
Pricing is unlocked once we know who you are. Take the 3-minute quiz and we'll match you to a US or EU dispensary based on your location and protocol fit.
- Live USD price range
- US & EU supplier shortlist
- Concierge sign-off on dosing
Indicative price range: $129–$193 USD