LY3437943 — the most advanced weight loss peptide in research. Triple GLP-1/GIP/Glucagon agonism, Phase 3 trial data, full titration protocol, and verified vendor pricing.
Retatrutide (LY3437943) is an investigational peptide developed by Eli Lilly currently in Phase 3 clinical trials. It is a triple receptor agonist — simultaneously activating GLP-1, GIP, and glucagon receptors — making it the most mechanistically comprehensive weight loss peptide currently in research.
Phase 2 data published in the New England Journal of Medicine demonstrated average body weight reductions of 24.2% over 48 weeks at the 12mg dose — surpassing both semaglutide (~15%) and tirzepatide (~22.5%) in direct comparison timeframes.
The addition of glucagon receptor agonism is the key differentiator from tirzepatide. Glucagon activation increases energy expenditure, directly burns fat through thermogenesis, and reduces liver fat.
Compound Name
Retatrutide
Also known as LY3437943. Developed by Eli Lilly. No approved brand name yet.
Compound Class
GGG Tri-Agonist
GLP-1 / GIP / Glucagon receptor co-agonist. The only triple agonist in late-stage trials.
Half-Life
~6 days
Once-weekly subcutaneous injection. Steady state achieved after approximately 5 weeks.
Trial Stage
Phase 3 (2026)
TRIUMPH Phase 3 program underway. Potential FDA filing expected 2027.
Peak Weight Loss
24.2% at 48 weeks
Phase 2 NEJM data at 12mg weekly. Highest reported weight loss of any investigational peptide.
Administration
Weekly SubQ
Subcutaneous injection, abdomen or thigh. Lyophilized powder requiring reconstitution with BAC water.
Mechanism of Action
How Retatrutide Works
Retatrutide works by simultaneously engaging three distinct receptor systems involved in metabolic regulation.
GLP-1 Receptor Agonism
GLP-1 receptor activation drives appetite suppression through hypothalamic receptors and delayed gastric emptying. It also improves insulin secretion in a glucose-dependent manner, reducing post-meal blood sugar spikes.
GIP Receptor Agonism
GIP agonism enhances insulin sensitivity in peripheral tissues and improves fat cell metabolism. The combination of GLP-1 + GIP produces synergistic effects on glucose regulation beyond either alone.
Glucagon Receptor Agonism — The Differentiator
Glucagon receptor activation directly increases energy expenditure by stimulating thermogenesis and fat oxidation. It also reduces liver fat — clinically significant for patients with MASH. This is why retatrutide surpasses tirzepatide in weight loss despite shorter trial durations.
Why Triple Agonism Matters
GLP-1 reduces intake, GIP improves metabolic efficiency, glucagon increases expenditure. Addressing all three simultaneously is why retatrutide's weight loss data outperforms compounds targeting only one or two pathways.
Comparison
Retatrutide vs Semaglutide vs Tirzepatide
How the three compounds compare across the metrics that matter most.
Metric
Semaglutide
Tirzepatide
Retatrutide ★
Receptor Targets
GLP-1 only
GLP-1 + GIP
GLP-1 + GIP + Glucagon
Peak Weight Loss
~15% (68 wks)
~22.5% (72 wks)
~24% (48 wks)
Metabolic Rate
Minimal increase
Modest increase
Significant increase
Liver Fat Reduction
Moderate
Good
Superior (glucagon)
Lean Mass Preservation
Some loss
Better than sema
Similar to tirze
GI Side Effects
Moderate
Similar to sema
Similar profile
Dosing Frequency
Once weekly
Once weekly
Once weekly
FDA Status
Approved
Approved
Phase 3 trials
Research Availability
✓ Available
✓ Available
✓ Available
Note on Comparison Data
These comparisons use different trial populations and timeframes — not head-to-head data. Phase 3 trials will provide more definitive comparative data.
Dosage Protocol
Retatrutide Dosage Guide
Retatrutide requires a titration protocol — starting at a low dose and increasing every 4 weeks. Rushing the titration is the most common mistake in research protocols.
Research data only. The following dosage ranges are sourced from published Phase 2 clinical trial data and community research reports. This is not medical advice.
Only advance to the next dose tier if the current dose is well tolerated with minimal nausea. Hold at current dose for an additional 2–4 weeks if GI symptoms are present.
Reconstitution Guide
Retatrutide is supplied as a lyophilized (freeze-dried) powder. It must be reconstituted with bacteriostatic water before use.
Wipe both vial tops with an alcohol swab. Allow to dry for 10 seconds.
3
Draw BAC water into syringe. For a 10mg vial: add 2mL BAC water = 5mg/mL concentration. For a 5mg vial: add 1mL = 5mg/mL.
4
Inject BAC water slowly down the inside wall of the peptide vial — do not spray directly onto the powder.
5
Swirl gently until fully dissolved. Do not shake. Solution should be clear and colorless.
6
Refrigerate immediately at 2–8°C. Label with reconstitution date. Use within 28–30 days.
7
To draw a dose: At 5mg/mL — for a 1mg dose draw 20 units on an insulin syringe. For 2mg draw 40 units. Inject SubQ into abdomen or thigh.
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Full Research Protocol
12-Week Starter Protocol
The most commonly referenced community starting protocol, based on Phase 2 titration data. Prioritizes tolerability over speed.
Weeks 1–4
0.5mg weekly
GI adaptation phase. Take with food initially. Expect minimal appetite effects.
Weeks 5–8
1mg weekly
First noticeable effects on appetite. Take on same day each week.
Weeks 9–12
2mg weekly
Primary therapeutic range for most researchers. Strong appetite suppression expected.
Weeks 13+
2mg – 4mg
Advance if well tolerated and weight loss has plateaued. Many maintain 2mg long-term.
Stacking with Other Peptides
Retatrutide can be combined with Tesamorelin for GH-axis support and lean mass preservation. BPC-157 is often co-run to protect the gut lining. Do not stack with other GLP-1 class peptides.
Safety & Side Effects
Side Effects & Considerations
Retatrutide's side effect profile is consistent with the GLP-1 class. The vast majority of reported effects are GI-related and dose-dependent.
Nausea
Most Common
Particularly during dose increases. Evening dosing with food reduces this significantly.
Reduced Appetite
Intended Effect
Can become extreme at higher doses. Ensure adequate protein (1g+ per lb lean body mass) to preserve muscle.
Vomiting / Diarrhea
Less Common
Typically occurs with too-rapid titration. Hold current dose 2 extra weeks if present.
Fatigue
Mild / Transient
Often occurs 24–48 hours post-injection. Diminishes with adaptation.
Muscle Loss Risk
Manage With Protein + Training
Resistance training and high protein intake are critical countermeasures.
Heart Rate Increase
Glucagon-related
Small but consistent increase (~2–4 bpm) observed in trials. Monitor with cardiac considerations.
Research Contraindications
Clinical trial exclusion criteria included: personal or family history of medullary thyroid carcinoma, MEN2, active pancreatitis, or severe GI disease. Research protocols should respect these exclusion criteria.
Where to Buy
Retatrutide Vendor Pricing
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Frequently Asked Questions
Retatrutide FAQ
What is the difference between retatrutide and tirzepatide?
Tirzepatide is a dual GLP-1/GIP agonist. Retatrutide adds a third target — the glucagon receptor. This directly increases energy expenditure and fat oxidation, which is why retatrutide's weight loss data (~24%) exceeds tirzepatide's (~22.5%) despite a shorter trial duration. Tirzepatide is FDA-approved; retatrutide is still in Phase 3 trials.
How long does it take to feel the effects?
Most research subjects report noticeable appetite suppression starting between weeks 3–6, typically when the dose reaches 1mg–1.5mg weekly. Significant weight loss is typically observed from weeks 8–12 onward. Steady-state blood levels are reached after approximately 5 weeks of weekly dosing.
What happens when you stop taking retatrutide?
Based on data from the semaglutide class, discontinuation typically leads to partial weight regain over 12–18 months as appetite returns to baseline. Many researchers plan for ongoing maintenance dosing or cyclical protocols.
Can retatrutide be stacked with other peptides?
Commonly stacked with: Tesamorelin, BPC-157, and MOTS-c. Do not stack with: Other GLP-1 class peptides (semaglutide, tirzepatide) — overlapping mechanisms with no added benefit and increased side effect risk.
What size vial should I buy for a 12-week protocol?
For the standard 12-week starter protocol: total dose = 4×0.5mg + 4×1mg + 4×2mg = 14mg total. Two 10mg vials covers this with buffer. Buying a 10mg vial is more cost-efficient per mg than multiple 5mg vials.
When will retatrutide be FDA-approved?
The TRIUMPH Phase 3 program is underway as of 2026. Based on typical FDA review timelines, an NDA filing is anticipated in 2027 with potential approval in 2027–2028. Phase 3 trials are evaluating obesity, type 2 diabetes, and MASH indications.