Triple-Agonist GLP-1 Medication
What is Retatrutide?
Retatrutide (LY3437943) is Eli Lilly's investigational triple-agonist that targets three receptors: GLP-1, GIP, and glucagon. In Phase 2 trials, participants achieved up to 24.2% body weight loss at 48 weeks, the highest ever recorded for an obesity medication.
24.2%
Max Weight Loss
~6 days
Half-Life
3
Receptor Targets
2027
Expected FDA
⚠️ Investigational Status: Retatrutide is NOT FDA-approved. It's currently in Phase 3 clinical trials. FDA approval is anticipated in 2027. Information on this page is based on published clinical trial data.
Retatrutide Resources
Interactive Tools
Dose Calculator & Plotter
TOOLVisualize retatrutide levels, track steady state, plan your titration with our free tool.
Units Calculator
TOOLConvert any retatrutide mg dose into exact insulin syringe units for your vial concentration.
Cost Calculator
TOOLEnter your vial price to see retatrutide cost per mg, week, month, and year.
Retatrutide Weight Loss Results
TRIUMPH trial data, expected weight loss timelines, and what the clinical evidence shows at each dose level.
Compounded Retatrutide: Legal Status
Retatrutide cannot be legally compounded under FDA 503A/503B. Here's what that means and what the risks are.
Guides & Articles
What Is Retatrutide?
Beginner's guide to the investigational triple-agonist: what it is, how it works, and what the research shows.
Reconstitution Guide
Step-by-step guide to mixing compounded retatrutide powder with bacteriostatic water.
Complete Dosing Guide
Standard titration protocol from 2mg to 12mg, Phase 2 trial schedules, and conservative approaches.
Microdosing Guide
Split dosing strategies for improved tolerability. Daily and twice-weekly protocols explained.
Dosing Schedule
Week-by-week titration calendar with printable schedule.
Retatrutide vs Tirzepatide
Head-to-head comparison of the triple-agonist vs dual-agonist. Efficacy, side effects, and mechanism.
Retatrutide vs Semaglutide
Triple-agonist vs single-agonist comparison. Clinical results, mechanisms, dosing, and availability.
Side Effects Guide
Common and serious side effects of retatrutide. Phase 2 clinical trial data and management strategies.
How Does Retatrutide Work?
Triple agonist mechanism explained. How GLP-1, GIP, and glucagon pathways combine for superior results.
Retatrutide Results
Clinical trial weight loss data, timelines, body composition changes, and metabolic improvements.
Is Retatrutide FDA Approved?
Current FDA status, TRIUMPH Phase 3 trial progress, and expected approval timeline.
How to Get Retatrutide
Three access routes: clinical trials, compounding pharmacies, and research peptides. Costs, risks, and legality.
Availability by Country
Global availability status, regulatory timelines, and when retatrutide will be commercially available.
How Retatrutide Works
Retatrutide's triple-agonist mechanism sets it apart from existing medications. While semaglutide (Ozempic, Wegovy) targets only GLP-1, and tirzepatide (Mounjaro, Zepbound) targets GLP-1 and GIP, retatrutide adds a third target: the glucagon receptor.
The Three Receptor Targets
GLP-1 (Glucagon-Like Peptide-1)
Reduces appetite, slows gastric emptying, improves insulin sensitivity. The same mechanism as semaglutide.
GIP (Glucose-Dependent Insulinotropic Polypeptide)
Enhances insulin secretion and may improve fat metabolism. Shared with tirzepatide.
Glucagon Receptor (Unique to Retatrutide)
Increases energy expenditure and promotes fat breakdown. This may explain the superior weight loss results.
The glucagon component is what makes retatrutide different. Glucagon normally raises blood sugar, but retatrutide's balanced activation of all three pathways produces net improvements in glucose control while also boosting metabolic rate, an effect not seen with GLP-1-only or dual-agonist medications.
Clinical Trial Results
The Phase 2 OASIS study published in The New England Journal of Medicine demonstrated unprecedented weight loss results across all dose groups.
| Dose Group | Weight Loss at 24 Weeks | Weight Loss at 48 Weeks |
|---|---|---|
| Placebo | -2.1% | -2.1% |
| 4mg weekly | -12.9% | -17.5% |
| 8mg weekly | -17.3% | -22.8% |
| 12mg weekly | -17.5% | -24.2% |
Key Finding: At the 12mg dose, 100% of participants lost at least 5% body weight, 93% lost at least 10%, and 63% lost at least 20% of their starting weight.
For context, tirzepatide's SURMOUNT-1 trial showed maximum weight loss of ~21% at 72 weeks, while semaglutide's STEP 1 trial demonstrated ~15% at 68 weeks. Retatrutide achieved 24.2% in just 48 weeks. For complete retatrutide clinical trial results and weight loss timelines, see our detailed guide.
Phase 3 TRIUMPH Trials
Phase 3 results are now coming in from the TRIUMPH series. TRIUMPH-OA, which enrolled adults with a BMI of 35 or higher and knee osteoarthritis, reported an average weight loss of 71.2 lbs over 68 weeks at the 9–12mg dose range. That works out to roughly 24% body weight reduction, consistent with the Phase 2 ceiling and confirming the results held up over a longer treatment period.
| Trial | Population | Duration | Result |
|---|---|---|---|
| OASIS (Phase 2) | Obesity (no T2DM) | 48 weeks | −24.2% body weight (12mg) |
| TRIUMPH-OA (Phase 3) | Obesity + knee OA (BMI ≥35) | 68 weeks | ~71.2 lbs avg (9–12mg) |
Beyond obesity, the TRIUMPH programme covers type 2 diabetes, sleep apnoea, fatty liver disease, and cardiovascular outcomes. Primary completion across the obesity arm is expected in early 2026. For a full breakdown of approval milestones, see Is Retatrutide FDA Approved?
Dosing Schedule
📋 Two dosing approaches: The schedule below is the Phase 2 clinical trial protocol from the OASIS study. Many users prefer microdosing (split dosing) for better tolerability, especially important with a triple-agonist's stronger effects.
Retatrutide follows a titration schedule similar to other GLP-1 medications, starting low and gradually increasing to minimize gastrointestinal side effects.
Standard Titration Schedule
2mg
Weeks 1-4
4mg
Weeks 5-8
8mg
Weeks 9-12
12mg
Week 13+
Prefer Microdosing?
Many users split their weekly dose into 2-3 smaller injections for smoother drug levels and fewer side effects. This is especially helpful with retatrutide's triple-agonist mechanism which can cause stronger GI effects.
Read the Microdosing Guide →Half-Life & Steady State
Retatrutide has a half-life of approximately 6 days (144 hours), similar to semaglutide (~7 days) and tirzepatide (~5 days). This supports once-weekly dosing.
What This Means
- Drug levels remain relatively stable between doses
- Steady state reached in 4-5 weeks at each dose
- Missing a dose doesn't cause immediate withdrawal
- Effects persist for days after stopping
Why It Matters for Dosing
- Wait 4+ weeks at each dose before increasing
- Previous dose still in system when you increase
- Side effects may emerge 1-2 weeks after dose change
- Use our calculator to visualize levels
💡 Pro tip: Use our retatrutide calculator to visualize how your drug levels build over time and predict when you'll reach steady state.
Common Side Effects
Like other GLP-1 agonists, retatrutide's most common side effects are gastrointestinal. These typically improve over time as your body adjusts.
Most Common (>10% of users)
- Nausea (especially during titration)
- Diarrhea
- Constipation
- Decreased appetite
- Vomiting
Less Common
- Injection site reactions
- Heartburn/acid reflux
- Fatigue
- Dizziness
- Hair thinning (reported anecdotally)
If side effects are severe, consider microdosing or staying at your current dose longer before increasing.
Ready to Plan Your Retatrutide Journey?
Use our free calculator to visualize your dosing schedule, predict when you'll reach steady state, and track your progress over time.
Frequently Asked Questions
Is retatrutide FDA approved?
No. As of 2026, retatrutide is not FDA-approved. It is an investigational drug in Phase 3 clinical trials (the TRIUMPH series). Phase 3 completion is expected in early 2026, with an FDA submission likely in late 2026 and potential approval in 2027. See our full FDA status guide for current milestones.
How much weight can you lose on retatrutide?
In the Phase 2 OASIS trial, participants on the 12mg dose lost an average of 24.2% of their starting body weight over 48 weeks. Every participant lost at least 5%, and 63% lost at least 20%. Phase 3 TRIUMPH-OA data shows roughly 71.2 lbs average loss at 68 weeks. Results depend on dose, adherence, and individual response. See our weight loss results guide for dose-by-dose timelines.
What makes retatrutide different from semaglutide and tirzepatide?
Retatrutide targets three receptors: GLP-1, GIP, and glucagon. Semaglutide targets only GLP-1; tirzepatide targets GLP-1 and GIP. The glucagon receptor component increases energy expenditure and promotes fat breakdown, which may explain the greater weight loss compared to both existing drugs. Detailed comparisons: retatrutide vs semaglutide and retatrutide vs tirzepatide.
What are the most common retatrutide side effects?
The most common side effects are gastrointestinal: nausea, diarrhea, vomiting, constipation, and reduced appetite. They are most pronounced during dose increases and typically ease after a few weeks at each level. In Phase 3 trials, 12–18% of participants discontinued due to side effects (vs. 4% on placebo). Splitting the weekly dose using a microdosing protocol can improve tolerability. See the full side effects guide.
What is the starting dose of retatrutide?
The Phase 2 clinical trial protocol started participants at 2mg once weekly for weeks 1–4, then titrated to 4mg, 8mg, and 12mg in 4-week intervals. No FDA-approved dosing protocol exists yet, since retatrutide is still investigational. See the complete dosing guide for standard and conservative titration options, and use the retatrutide calculator to model your schedule.
When will retatrutide be available?
Eli Lilly expects Phase 3 trials to complete in early 2026. A positive readout would allow submission of an NDA to the FDA, with approval possibly following in 2027 and commercial availability shortly after. For current regulatory timelines by country, see retatrutide availability.
Can you get retatrutide now?
Not through a standard prescription. Access is currently limited to clinical trial enrolment or, informally, research peptide suppliers (which carries significant legal and safety risks). Retatrutide cannot be legally compounded under FDA 503A/503B rules. See how to get retatrutide and compounded retatrutide legal status for full details.
Related Resources
⚠️ Medical Disclaimer: The information on this page is for educational purposes only and does not replace professional medical advice, diagnosis, or treatment. Retatrutide is an investigational drug and is not approved by the FDA. Do not start, stop, or adjust any medication without consulting a qualified healthcare provider.