Peptide Name
Retatrutide (LY3437943)
Updated April 2026
Written by Garret Grant
Founder & Lead Researcher · B.S. Civil Engineering, UCLA
Last updated: April 2026
Complete Retatrutide dosing protocol and safety guide covering the retatrutide titration schedule, retatrutide reconstitution, retatrutide side effects, and clinical trial outcomes. Retatrutide is a once-weekly investigational triple agonist frequently compared with Cagrilintide, and readers exploring that pairing can also review the Cagrilintide + Retatrutide stack protocol. This page is built to help you understand what the dose ranges, tables, and trial results actually mean before you dig into the details.
Half-life
~6 days
Dose range
1 mg to 12 mg weekly
Status
Phase 3 investigational
Developer
Eli Lilly and Company
Need to calculate reconstitution and dosing units? Use the peptide reconstitution calculator.
Peptide Name
Retatrutide (LY3437943)
Use Case
Research readers usually look at retatrutide for weight-loss and metabolic research because it affects appetite, blood-sugar signaling, and calorie burn at the same time.
Category / Class
Metabolic triple agonist. That means retatrutide acts on GLP-1, GIP, and glucagon receptors rather than just one pathway.
Half-Life
~6 days
Dosing Frequency
Once weekly (subcutaneous injection)
Dose Range
1 mg - 12 mg per week
Titration Schedule
1 mg -> 2 mg -> 4 mg -> 6 mg -> 9 mg -> 12 mg, typically increased every 4 weeks
Common Vial Sizes
5 mg, 10 mg, 20 mg, 30 mg
Route of Administration
Subcutaneous (SubQ)
Regulatory Status
Retatrutide is still investigational. Lilly says it has not been approved by any regulatory agency as of March 2026, and it remains in Phase 3 clinical trials.
Developer
Eli Lilly and Company
Key Stat
In clinical trials, higher-dose retatrutide produced strong weight-loss results: up to 24.2% at 48 weeks in Phase 2 and up to 28.7% at 68 weeks in Phase 3 TRIUMPH-4.
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Retatrutide (LY3437943) is an investigational once-weekly peptide from Eli Lilly being studied for obesity and related metabolic conditions. What makes retatrutide different is that it works on three hormone pathways at once: GLP-1, GIP, and glucagon.

For most readers, that matters because those three pathways are linked to appetite, blood-sugar control, and energy expenditure. In plain terms, retatrutide is being studied as a broader metabolic therapy than semaglutide (GLP-1 only) or tirzepatide (GLP-1 + GIP).
Structurally, retatrutide is a 39-amino acid single-chain peptide with a C20 fatty diacid attachment that helps it bind to albumin in the bloodstream. That longer circulation time is why retatrutide half-life is about 6 days and why the protocol uses once-weekly dosing.
Retatrutide is currently being studied across Eli Lilly's Phase 3 TRIUMPH and TRANSCEND programs in obesity, type 2 diabetes, knee osteoarthritis pain, obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease (MASLD). Lilly released TRIUMPH-4 topline osteoarthritis results on December 11, 2025 and announced first Phase 3 type 2 diabetes topline results from TRANSCEND-T2D-1 on March 19, 2026. Lilly says additional results from the retatrutide clinical trial program are expected over the next year.
Retatrutide is not FDA-approved and is currently available only through clinical trials. All information on this page is for educational and research reference purposes only.
Retatrutide works through three receptor pathways at the same time. The simplest way to think about it is this: one pathway helps you feel full, one improves how the body handles glucose and stored fuel, and one may increase energy expenditure.

This pathway slows digestion and helps you feel full longer, which is one reason retatrutide can reduce appetite. It is the same general pathway used by semaglutide, so readers coming from GLP-1 research will recognize this part of the mechanism.
This pathway appears to help with insulin response and how the body handles fat and energy. You do not need to remember the receptor biology to use the page: the practical takeaway is that GIP is part of why retatrutide is studied as a broader metabolic compound rather than a single-pathway appetite suppressant.
This is the extra pathway that separates retatrutide from tirzepatide. It may help explain the stronger liver-fat and weight-loss data because glucagon receptor activity is linked to higher energy expenditure and fat oxidation.
Retatrutide's engineered potency ratio matters mainly because one peptide is affecting appetite, glucose handling, and calorie burn at the same time. Think of it as a three-lever system rather than a single on-off switch.
Use this retatrutide dosing protocol as a slow escalation plan, not a dose you jump into. The retatrutide starting dose in clinical trials is 1 mg once weekly, and the retatrutide titration schedule climbs over time so tolerance can build before higher doses are reached.
Phase 1 - Initiation
Weeks 1-4
1 mg once weekly
Starting dose to assess initial tolerance. Minimal metabolic effects expected at this dose.
Phase 2 - Early Escalation
Weeks 5-8
2 mg once weekly
First meaningful dose increase. GI side effects (nausea) may begin.
Phase 3 - Mid Escalation
Weeks 9-12
4 mg once weekly
Appetite suppression typically becomes noticeable. Weight loss begins accelerating.
Phase 4 - High Escalation
Weeks 13-16
6 mg once weekly
TRIUMPH Phase 3 added this intermediate step (not present in Phase 2 trials).
Phase 5 - Therapeutic Range
Weeks 17-20
9 mg once weekly
Phase 3 target dose. Significant weight loss expected.
Phase 6 - Maximum Studied Dose
Weeks 21+
12 mg once weekly
Maximum dose studied in clinical trials. 24.2% average weight loss at 48 weeks (Phase 2). 28.7% at 68 weeks (Phase 3, TRIUMPH-4).
Important Titration Notes
Titration pacing matters. In the Phase 2 NEJM trial (2023), GI side effect rates nearly doubled when participants were assigned directly to 8 mg instead of gradually titrating from 1-2 mg.
Dose flexibility: Trial protocols allowed participants to stay at the current dose for an extra 2-4 weeks when nausea or other GI side effects were significant.
Phase 3 dose levels: TRIUMPH evaluates 4 mg, 9 mg, and 12 mg as target maintenance doses.
Missed dose guidance: If a scheduled dose is missed, it can be taken within 5 days. If more than 5 days have passed, skip it and resume on the next scheduled injection day.
This retatrutide reconstitution guide answers two separate questions: how much bacteriostatic water to add to the vial, and how many syringe units match your target dose after mixing. If you are wondering how to reconstitute retatrutide, read across your vial-size row first, then match the final concentration to your dose.
Vial Size: 5 mg
BAC Water: 1.0 mL
Concentration: 5,000 mcg/mL (5.0 mg/mL)
1 mg: 0.20 mL (20 units)
2 mg: 0.40 mL (40 units)
4 mg: 0.80 mL (80 units)
8 mg: N/A - exceeds vial
12 mg: N/A
Vial Size: 10 mg
BAC Water: 2.0 mL
Concentration: 5,000 mcg/mL (5.0 mg/mL)
1 mg: 0.20 mL (20 units)
2 mg: 0.40 mL (40 units)
4 mg: 0.80 mL (80 units)
8 mg: Requires 2 vials
12 mg: Requires 2-3 vials
Vial Size: 20 mg
BAC Water: 2.0 mL
Concentration: 10,000 mcg/mL (10.0 mg/mL)
1 mg: 0.10 mL (10 units)
2 mg: 0.20 mL (20 units)
4 mg: 0.40 mL (40 units)
8 mg: 0.80 mL (80 units)
12 mg: 1.20 mL - split draw
Vial Size: 30 mg
BAC Water: 3.0 mL
Concentration: 10,000 mcg/mL (10.0 mg/mL)
1 mg: 0.10 mL (10 units)
2 mg: 0.20 mL (20 units)
4 mg: 0.40 mL (40 units)
8 mg: 0.80 mL (80 units)
12 mg: 1.20 mL - split draw

Retatrutide side effects look broadly similar to other incretin-based therapies, but the easiest way to understand them is in two buckets: stomach-related symptoms during dose escalation and a separate skin-sensation signal at higher doses.
Common gastrointestinal effects: In Phase 2 (NEJM), nausea occurred in up to 25% of participants at 12 mg, diarrhea up to 23%, vomiting up to 26%, and constipation up to 16%. These issues were most common during escalation and were usually mild to moderate.
Cardiovascular signal: Resting heart rate increased by about 5-10 bpm on average, peaking near week 24 and easing by weeks 36-48. No increase in serious cardiovascular events was reported.
Dysesthesia in Phase 3: TRIUMPH-4 on December 11, 2025 reported dysesthesia, meaning unusual skin sensitivity or tingling, in about 20.9% at the highest dose.
Liver enzymes: Temporary ALT/AST elevations occurred in a minority of participants and were generally linked to dose increases.
Injection site reactions: Redness, itching, and small nodules were observed in roughly 5-15% of participants.
Discontinuation: In Phase 2, 6-16% stopped because of adverse events versus 0% on placebo. Slow titration improved adherence.
Retatrutide clinical trial results are strongest in obesity studies, with additional signals in type 2 diabetes, liver-fat reduction, and osteoarthritis-related pain. The simplest way to read the table is that higher-dose retatrutide has produced unusually large weight-loss effects for an investigational once-weekly peptide, but the program is still ongoing and not yet FDA-approved.
Jastreboff et al., NEJM 2023
Phase 2 • 48 weeks
338 adults with obesity (no diabetes)
12 mg: -24.2% body weight; 8 mg: -22.8%; 4 mg: -17.5%. 100% of 8 mg and 12 mg participants lost >=5%.
TRIUMPH-4, Eli Lilly 2025
Phase 3 • 68 weeks
Adults with obesity + knee osteoarthritis
12 mg: -28.7% body weight; 9 mg: similar results. Also significant pain reduction (WOMAC -4.5 points).
Rosenstock et al., Lancet 2023
Phase 2 • 36 weeks
Adults with type 2 diabetes
Up to -16.9% weight loss. HbA1c improved by -2.2%. 82% reached HbA1c <=6.5%.
Sanyal et al., Nature Medicine 2024
Phase 2 substudy • 48 weeks
Adults with MASLD and >=10% liver fat
Up to 82% relative reduction in liver fat at 24 weeks.

As of April 5, 2026, Lilly's retatrutide Phase 3 work spans the TRIUMPH obesity program and the TRANSCEND-T2D diabetes program, with additional studies in obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and MASLD. TRIUMPH-4 topline osteoarthritis results were released on December 11, 2025, and Lilly announced positive TRANSCEND-T2D-1 topline results on March 19, 2026. Lilly says additional results from the retatrutide clinical trial program are expected over the next year, but retatrutide remains investigational and not approved by any regulatory agency.
Use the storage table as a priority guide. For most readers, the main rule is simple: keep reconstituted retatrutide refrigerated at 2-8C, protect it from light, and plan to use it within 2-4 weeks.
Lyophilized powder is more temperature-tolerant than mixed solution, which is why short shipping exposure is usually less concerning than poor storage after reconstitution.
Lyophilized (powder, sealed)
-20C (-4F) or below (freezer)
Long-term - up to 12+ months
Lyophilized (powder, sealed)
2-8C (35.6-46.4F) (refrigerator)
Several months
Lyophilized (powder, sealed)
Room temperature (during shipping)
Stable for several weeks - peptide powders tolerate short-term temperature fluctuations
Reconstituted (solution)
2-8C (35.6-46.4F) (refrigerator)
Use within 2-4 weeks
Reconstituted (solution)
-20C (-4F) (frozen aliquots)
3-4 months
Avoid repeated freeze-thaw cycles, and if long-term storage is necessary, freeze single-use aliquots rather than the same vial over and over. Bacteriostatic water (0.9% benzyl alcohol) is preferred for multi-dose workflows.
Retatrutide vs tirzepatide vs semaglutide is mainly a question of how many metabolic pathways each compound activates. Semaglutide is single-pathway, tirzepatide is dual-pathway, and retatrutide is triple-pathway, which may help explain why retatrutide has shown stronger weight-loss and liver-fat results in trials.
Receptor Targets
Retatrutide: GLP-1 + GIP + Glucagon (triple)
Tirzepatide: GLP-1 + GIP (dual)
Semaglutide: GLP-1 only (single)
Half-Life
Retatrutide: ~6 days
Tirzepatide: ~5 days
Semaglutide: ~7 days
Dosing Frequency
Retatrutide: Once weekly
Tirzepatide: Once weekly
Semaglutide: Once weekly
Max Studied Dose
Retatrutide: 12 mg/week
Tirzepatide: 15 mg/week
Semaglutide: 2.4 mg/week
Peak Weight Loss (Trials)
Retatrutide: -28.7% at 68 weeks (Phase 3)
Tirzepatide: -22.5% at 72 weeks (SURMOUNT-1)
Semaglutide: -15.8% at 68 weeks (STEP-1)
FDA Status (Apr 2026)
Retatrutide: Investigational - Phase 3
Tirzepatide: Approved (obesity + T2D)
Semaglutide: Approved (obesity + T2D)
Liver Fat Reduction
Retatrutide: Up to 82% reduction (substudy)
Tirzepatide: Significant reduction
Semaglutide: Moderate reduction
Unique Advantage
Retatrutide: Triple agonism increases energy expenditure via glucagon
Tirzepatide: Dual agonism balances efficacy and tolerability
Semaglutide: Longest clinical track record, CV outcomes data (SELECT trial)
That extra glucagon activity is also one reason retatrutide is harder to compare on tolerability alone. The same pathway that may increase energy expenditure may also help explain the dysesthesia signal seen in Phase 3.
These compounds are not interchangeable. Reconstitution math, dose ranges, approval status, and evidence maturity differ for each one.
See the tirzepatide protocol and semaglutide protocol for compound-specific guides.
Before combining compounds, read the full stacking safety guide on PepPal.
Stack: Metabolic Research Stack
Dual-pathway metabolic modulation targeting GLP-1/GIP/glucagon signaling (retatrutide) and mitochondrial signaling (MOTS-c) in preclinical research models.
MOTS-c is a mitochondria-derived peptide studied for exercise-mimetic effects and metabolic regulation. Combined with retatrutide, this stack represents a complementary multi-pathway research approach.
See the compound-specific MOTS-c protocol for additional context.
View full Metabolic Research Stack protocolGet notified when new dosing references, stack breakdowns, and calculator-driven research pages go live. No multi-step signup, just the email field.
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The starting dose of retatrutide in clinical trials is 1 mg once weekly for the first 4 weeks. That low starting point gives the body time to adjust before the retatrutide titration schedule moves higher.
Retatrutide half-life is about 6 days, which is why the dosing schedule is usually once weekly. The technical reason is albumin binding, but the practical takeaway is simply that retatrutide stays active long enough to support weekly dosing.
In the Phase 2 trial (NEJM, 2023), participants on 12 mg lost an average of 24.2% body weight at 48 weeks. Lilly released Phase 3 TRIUMPH-4 topline results on December 11, 2025 showing weight loss up to 28.7% at 68 weeks. Results were dose-dependent.
To reconstitute retatrutide, add bacteriostatic water based on the vial size and the concentration you want, then use the table to match your dose to syringe units. For example, a 10 mg vial mixed with 2.0 mL gives 5,000 mcg/mL. Inject the water down the vial wall, swirl gently, do not shake, refrigerate at 2-8C, and use within 2-4 weeks.
No. As of April 5, 2026, retatrutide is not FDA-approved. Lilly says it has not been approved by any regulatory agency and remains investigational in ongoing Phase 3 trials.
The most common retatrutide side effects are stomach-related: nausea, diarrhea, vomiting, and constipation, especially during dose escalation. At the highest dose in Phase 3, some participants also reported dysesthesia, which means unusual skin sensitivity or tingling.
Retatrutide is a triple agonist, tirzepatide is a dual agonist, and semaglutide is a single agonist. In plain terms, retatrutide acts on more pathways at once, which may help explain the stronger weight-loss results seen so far, but retatrutide is still investigational while tirzepatide and semaglutide are FDA-approved.
Research-grade retatrutide is commonly available in 5 mg, 10 mg, 20 mg, and 30 mg vial sizes. Vial size affects reconstitution math and doses per vial.
It depends on vial size and target concentration. Common mixes: 5 mg + 1.0 mL = 5,000 mcg/mL; 10 mg + 2.0 mL = 5,000 mcg/mL; 20 mg + 2.0 mL = 10,000 mcg/mL; 30 mg + 3.0 mL = 10,000 mcg/mL. Calculator: https://www.peppal.app/calculator
The maximum weekly dose studied is 12 mg. In Phase 2, 12 mg reached -24.2% at 48 weeks, and in Phase 3 TRIUMPH-4 up to -28.7% at 68 weeks.
Store reconstituted retatrutide at 2-8C, protected from light, and use within 2-4 weeks. Lyophilized powder is generally stored at -20C for long-term stability. Avoid repeated freeze-thaw cycles.
TRIUMPH is Eli Lilly's Phase 3 obesity-focused retatrutide program. It includes obesity or overweight studies plus work in knee osteoarthritis pain, obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and MASLD. Lilly's separate TRANSCEND-T2D Phase 3 program covers type 2 diabetes.
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Disclaimer: The information on this page is for educational and research reference purposes only. Retatrutide is an investigational compound not approved by the FDA. No compounds discussed on this site are intended for human consumption. This is not medical advice. Consult a qualified healthcare professional before considering any peptide protocol. Protocol data is compiled from published clinical trials, peer-reviewed literature, and community research documentation.
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