Weight Management

Retatrutide

LY3437943

Lilly triple GLP-1/GIP/glucagon analog (LY3437943). Phase 2/3 numbers are large. Not an FDA-approved US obesity pen on this catalog date. Gray-market “reta” is not TRIUMPH-4 material. Do not treat NAFLD from this page.

TRIUMPH Phase 3 ongoing - Phase 3 TRIUMPH-4 results reported Dec 2025; not yet FDA-approved

Reviewed by CalcMyPeptide Editorial Team

·Last updated: August 2026·Evidence: Emerging·3 peer-reviewed citations

Typical research dose

1-12 mg/week

Frequency

1× weekly

Half-life

144 hours (~6 days)

Common vials

5 mg / 10 mg

CAS

2381089-83-2

Molecular weight

4731.34 g/mol

Use-case scores

0–10 against the evidence we have, not a gym ranking. Hidden domains do not apply here.

Metabolic / weight8/10
Phase 2 plus TRIUMPH-4 Phase 3 readouts. Ceiling 8 for Phase 2–3. Not 8.5–9 until there is a US label. Glucagon arm is extra efficacy and extra heart-rate/glycogen theoretical cost.

Compound card

Sequence: Triple GLP-1/GIP/glucagon analog (LY3437943)
Class: Once-weekly triple agonist (not FDA-approved as of this review)
Formula: C221H342N46O68
Status: TRIUMPH Phase 3 ongoing - Phase 3 TRIUMPH-4 results reported Dec 2025; not yet FDA-approved

Dose it

10 mg + 2 mL BAC water → 5 mg/mL · 1000 mcg ≈ 20 units (U-100)

Open in calculator

How it works

Retatrutide (LY3437943) is a triple agonist peptide that simultaneously activates GLP-1, GIP, and glucagon receptors - making it the first triple-action incretin therapy. While GLP-1 and GIP agonism provide the established weight loss mechanisms (appetite suppression, insulin sensitization, gastric slowing), the addition of glucagon receptor activation introduces a third metabolic lever: increased hepatic fatty acid oxidation and energy expenditure.

Phase II trial data demonstrated up to 24.2% body weight reduction at 12 mg, already surpassing semaglutide and tirzepatide. In December 2025, Phase III TRIUMPH-4 results (68 weeks, adults with obesity + knee osteoarthritis) showed 28.7% weight loss at the 12 mg dose and 26.4% at 9 mg - setting a new benchmark for any pharmacological weight loss agent. Retatrutide has a 6-day half-life, supporting once-weekly dosing.

Source: PMID: 37351564 (Phase II)

Goal context

Triple is not “semaglutide plus two”

GLP-1, GIP, and glucagon are different receptors. The glucagon piece is why energy-expenditure language shows up. It is also why this is not a casual DIY escalation.

Background & History

Retatrutide (LY3437943) is Lilly’s triple GLP-1/GIP/glucagon analog. Phase 2 NEJM 2023 numbers are large. TRIUMPH is ongoing. Gray-market “reta” is not trial material. Glucagon-arm hepatic-fat observations are not a MASH indication on this page.

Key Clinical Metrics

Peak Weight Loss

28.7%

Achieved in Phase 3 TRIUMPH-4 trial at the 12mg target dose.

Receptor Targets

GLP-1, GIP, Glucagon

Triple-agonist action uniquely increases lipolysis and resting energy expenditure.

Hepatic Fat Clearance

100% Resolution

Unmatched liver fat clearance due to direct glucagon agonism.

Published Trial Data

Phase 3 (TRIUMPH-4)

Retatrutide in OA and Obesity

Demonstrated an unprecedented 28.7% average body weight loss at the 12 mg dose, setting a new clinical benchmark for pharmacological agents.

Source

Phase 2 (TRIUMPH-1 & 2)

Triple-Hormone Receptor Agonist for Obesity

Showed up to 24.2% mean body weight reduction at 48 weeks, indicating an incredibly rapid and sustained weight loss trajectory.

Source

Phase 2

Hepatic Steatosis Clearance

Showed rapid clearance of liver fat (hepatic steatosis) in 100% of analyzed patients due to the strong glucagon receptor activation mechanism.

Source

Research Use Cases

✓Identity: triple agonist vs tirzepatide vs semaglutide
✓Why Phase 2 percents do not transfer to an unknown cake
✓Not a NAFLD/NASH or T2D treatment page

Dosing

Phase	Dose	Frequency	Notes
Initiation (Weeks 1-4)	1.0 - 2.0 mg	once weekly	Lower start than other GLP-1s due to triple receptor potency.
Escalation	4.0 / 6.0 / 9.0 mg	once weekly	Escalate every 4 weeks based on tolerability.
Maximum Dose	12.0 mg	once weekly	Phase II/III maximum studied dose. Showed ~24-28% weight loss.

Administration

Route / form

Subcutaneous injection

Timing

Once weekly.

Empty stomach?

No - Food timing is not critical.

Retatrutide: Lilly trial product (no US pen yet) vs Compounded / research vial

Lilly trial product (no US pen yet)

Bioavailability

There is no US commercial pen on this leaf’s date. Trial material is a finished investigational product, not a research vial you BAC-reconstitute.

Dose note

Trial doses were milligrams once weekly on finished investigational product. A gray-market cake is not that material. Do not invent a pen click-chart for a US product that is not for sale.

Advantages

Phase 2/3 numbers describe Lilly trial product. That is a real program. It is not a research-chem SKU.
No reconstitution step. No BAC water. No fake 5 mg vial chart.
TRIUMPH-4 is a Phase 3 readout. Phase 3 is not a commercial FlexPen in a US pharmacy.

Considerations

Not FDA-approved as a finished US obesity pen on this page’s date. Phase 3 is not a label.
Pens do not go in the reconstitution calculator.

Compounded / research vial

Bioavailability

Same INN story is not the same product. A lyophilized cake has no device, no STEP/SURMOUNT pharmacovigilance, and often no trustworthy fill. Do not paste branded F% onto a COA you have not read.

Dose note

If you have a gray-market cake, do milligram weekly math from the COA. Trial doses were 1–12 mg weekly, not micrograms. This is not TRIUMPH-4 material. This column is the only one that gets bacteriostatic water. Pens do not. Confirm milligrams, not micrograms. Weekly incretin math is not a 250 mcg BPC chart.

Advantages

If you actually have a cake, vial math is the job this site will do.
Gray-market “reta” identity is unverified. Do not treat it as Lilly trial fill.

Considerations

A cake is not the pen. Identity, sterility, and dose accuracy are on you and the compounder.
Do not stack with another GLP-1/GIP agonist.
Boxed-warning class (MTC/MEN2) still applies to the receptor, not only to the brand name.

Recommendation: Retatrutide: trial product is not a US pen you can buy, and a gray-market cake is not TRIUMPH material. Do not BAC-reconstitute a fantasy device. Cakes still need honest vial math if that is what you bought.

Timeline

Months 1-2

Immediate appetite reduction and increased energy expenditure due to glucagon agonism.

Months 6-12

Steep continuous weight loss - less plateauing observed vs. mono/dual agonists in trials.

Who it is for

Obesity / Severe Overweight

High

Phase III trials show ~24-28% body weight reduction - currently the most potent agent in clinical development.

MASH (Metabolic Liver Disease)

High

Glucagon receptor agonism rapidly clears hepatic steatosis; strong early trial signal.

Reconstitution

Vial	Water	Concentration	Example dose
Research/compounded cake (unlabeled)	Vendor-dependent	Do the math on the COA	Trial doses were milligrams weekly, not micrograms. Do not copy a BPC unit chart.

Change vial size or water volume? Open the reconstitution calculator.

Safety & Considerations

Retatrutide is an investigational drug in Phase III clinical trials (TRIUMPH program). It is not yet FDA-approved. Compounded versions are available through licensed pharmacies. Side effect profile is consistent with other incretin therapies (nausea, diarrhea, decreased appetite - predominantly during dose escalation). Not recommended during pregnancy.

Regulatory & Legal Status

FDA Status (US)

Phase 3

TRIUMPH Phase 3 ongoing - Phase 3 TRIUMPH-4 results reported Dec 2025; not yet FDA-approved

WADA Status (2026)

Not Listed

Not currently on the WADA 2026 Prohibited List. Policies may change - verify before competition.

Classification

Investigational

US Compounding: Available via licensed pharmacy Rx

⚠️ This information is for educational purposes only and may not reflect the most current regulatory updates. Always verify with official FDA, WADA, and jurisdiction-specific sources before use.

Limits of current evidence

Not an FDA-approved finished product on this review date. Phase 3 is not a label.
Glucagon receptor agonism is the extra lever and the extra monitoring conversation (HR, glycogen, lean mass).
Gray-market “retatrutide” identity is unverified. Parent trial material is not a 10 mg cake.

Verdict

Retatrutide is the triple-agonist Lilly program, not a research-chem toy. Phase 3 numbers are large. It is not an approved US obesity pen on this leaf’s date. Do not treat a gray-market “reta” vial as TRIUMPH-4.

Interactions & Contraindications

Investigational. Same MTC/MEN2 class caution as GLP-1 RAs. Glucagon agonism can move glucose. Not combined with other incretin agents.

Synergies & Common Stacks

+ Tirzepatide →

Do not stack incretins. Two agonists is GI risk without a labeled combo.

Retatrutide vs. Tirzepatide

Canonical comparison: Retatrutide vs Tirzepatide

Attribute	Retatrutide	Tirzepatide
Mechanism	GLP-1 + GIP + Glucagon (triple)	GIP + GLP-1 (dual)
Peak Weight Loss	~28.7%+ (Phase 3 TRIUMPH)	22.5% (SURMOUNT-1)
FDA Status	Phase 3 - not approved	Approved (Mounjaro® / Zepbound®)
Availability	Investigational / compounded	Branded + compounded
Safety Data	Phase 3 emerging	Extensive Phase 3 + 3yr real-world

Verdict: Retatrutide outperforms tirzepatide on weight loss endpoints in Phase 3 data. However, tirzepatide is FDA-approved with 3+ years of real-world safety data. Choose retatrutide only through a knowledgeable prescriber comfortable with investigational protocols.

Appears in goal guides

Goal guides are maps, not clinic protocols. A mention here is not a treatment plan.

The Furnace: Advanced Lipolysis

Thyroid and pancreas cytomax plus Tesamorelin, AOD-9604, Retatrutide, and 5-amino-1MQ. Visceral fat stack, not a stimulant fat burner.

View Protocol →

Frequently Asked Questions

Pen or compounded vial?▼

There is no US commercial retatrutide pen on this leaf’s date. Phase 3 numbers describe Lilly trial product. A gray-market cake is not TRIUMPH-4 material. If you have a cake, do milligram weekly math from the COA. Do not invent a click-chart.

How is retatrutide different from tirzepatide?▼

Retatrutide is a triple agonist (GLP-1 + GIP + glucagon), while tirzepatide is a dual agonist (GLP-1 + GIP only). The additional glucagon receptor activation increases energy expenditure and hepatic fat oxidation. Phase III TRIUMPH-4 results (Dec 2025) showed 28.7% weight loss at 12 mg, compared to tirzepatide's 22.5% - a meaningful clinical difference.

What is the retatrutide dose escalation?▼

Phase II protocol: Start at 1 mg/week, escalate monthly through 2, 4, 8, and 12 mg/week. Use our GLP-1 Scheduler for week-by-week calculations.

Is retatrutide FDA-approved?▼

No. Retatrutide is in Phase III trials under the TRIUMPH program. Phase III TRIUMPH-4 results were reported in December 2025, showing 28.7% weight loss at the 12 mg dose at 68 weeks. FDA submission is anticipated once the broader TRIUMPH trial readouts are complete in 2026.

References

Rosenstock et al. “"Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes".” The Lancet (2023). PMID: 37385280
Jastreboff et al. “"Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial".” New England Journal of Medicine (2023). PMID: 37366315
Jastreboff AM, et al. “Triple-hormone-receptor agonist retatrutide for obesity - a phase 2 trial.” N Engl J Med (2023). PMID: 37351564

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