Research reference only — not medical advice. Products sold by Clean Peptides are intended strictly for laboratory research purposes and are not for human or veterinary use. This guide compiles information from Clean Peptides together with independent educational material from PeptideWiki, for research reference only.
What Is Retatrutide?
Investigational compound warning: Retatrutide (LY3437943) is not FDA-approved. It is an investigational compound currently in Phase 3 clinical trials (the TRIUMPH program). All dosing information in this guide is derived from a single Phase 2 trial and community research protocols — not from an approved drug label.
Retatrutide is an investigational triple hormone receptor agonist developed by Eli Lilly, and the first compound designed to simultaneously activate three incretin and metabolic hormone receptors: GLP-1, GIP and glucagon. This triple mechanism distinguishes it from single agonists like Semaglutide (GLP-1 only) and dual agonists like Tirzepatide (GLP-1 + GIP).
The addition of glucagon receptor agonism is the novel element. While GLP-1 and GIP suppress appetite and enhance insulin secretion, glucagon increases energy expenditure, promotes hepatic fat oxidation and stimulates thermogenesis. In the Phase 2 trial, Retatrutide at 12 mg per week produced 24.2% body weight loss at 48 weeks in study participants — the largest ever reported in an obesity drug trial.
Key characteristics
- Triple receptor agonist — simultaneously activates GLP-1, GIP and glucagon receptors.
- GLP-1 receptor — suppresses appetite, slows gastric emptying, enhances glucose-dependent insulin secretion.
- GIP receptor — improves insulin sensitivity and lipid metabolism.
- Glucagon receptor (novel) — increases energy expenditure, promotes hepatic fat oxidation and thermogenesis.
- Once-weekly injection — administered subcutaneously, estimated half-life of ~6 days.
- Investigational status — currently in Phase 3 trials; approval not expected before late 2026–2027.
Phase 2 Trial Results by Dose Group
The pivotal Phase 2 trial (Jastreboff et al., NEJM 2023) enrolled 338 adults, randomized to placebo or 1, 4, 8 or 12 mg weekly for 48 weeks, all using a titration schedule.
| Group | Mean Weight Loss | ≥5% Loss | ≥10% Loss | ≥15% Loss |
|---|---|---|---|---|
| Placebo | −2.1% | 27% | 9% | 5% |
| 1 mg | −8.7% | 64% | 34% | 19% |
| 4 mg | −17.1% | 93% | 75% | 57% |
| 8 mg | −22.8% | 100% | 93% | 83% |
| 12 mg | −24.2% | 100% | 93% | 83% |
Titration Schedule
Retatrutide requires gradual dose escalation over the first 12 weeks to minimize gastrointestinal side effects. All doses are once weekly, subcutaneous.
| Period | Weekly Dose | Duration |
|---|---|---|
| Step 1 | 2 mg | Weeks 1–4 |
| Step 2 | 4 mg | Weeks 5–8 |
| Step 3 | 8 mg | Weeks 9–12 |
| Maintenance (12 mg target) | 12 mg | Week 13+ |
Lower targets (4 mg or 8 mg) follow the same step-1/step-2 pattern, simply stopping escalation at the target dose. Do not skip titration — starting at the full target dose is the single most common mistake and leads to severe nausea, vomiting and diarrhea. Some researchers start even lower (0.5–1 mg for the first 1–2 weeks) to further reduce initial GI effects.
Retatrutide vs Semaglutide vs Tirzepatide
| Feature | Retatrutide | Semaglutide | Tirzepatide |
|---|---|---|---|
| Receptors | GLP-1 + GIP + Glucagon | GLP-1 only | GLP-1 + GIP |
| FDA Status | Not approved (Phase 3) | Approved | Approved |
| Max dose (trial) | 12 mg/week | 2.4 mg/week | 15 mg/week |
| Peak weight loss (trial) | 24.2% at 48 wk | ~15–17% at 68 wk | ~22.5% at 72 wk |
| Half-life | ~6 days | ~7 days | ~5 days |
| Titration period | 12 weeks | 16–20 weeks | 16–20 weeks |
Cross-trial figures come from different populations and durations and are indicative, not head-to-head.
Reconstitution & Dosing (with the supplied 3 ml bacteriostatic water)
Clean Peptides also offers Retatrutide as a pre-filled click pen requiring no reconstitution — see the dedicated Retatrutide Pen guides linked below for a clicks-to-mg schedule.
Every Clean Peptides Retatrutide vial ships with 3 ml of bacteriostatic water (0.9% benzyl alcohol). All figures below assume reconstitution with the full 3 ml. On a standard U-100 insulin syringe, 100 units = 1 ml. Quick formula: concentration = vial strength ÷ 3 ml, and units to draw = dose (mg) × 300 ÷ vial strength (mg).
How to reconstitute
- Wash your hands and lay out the vial, the 3 ml bacteriostatic water, an insulin syringe and alcohol swabs on a clean surface.
- Flip off the caps and swab both rubber stoppers with alcohol; let them air-dry 10–15 seconds.
- Draw the full 3 ml of bacteriostatic water (in three 1 ml passes with an insulin syringe, or one pass with a 3 ml syringe).
- Add the water slowly, angling the needle so it runs down the inside glass wall — never squirt it directly onto the powder.
- Dissolve gently — let the vial sit 1–2 minutes, then swirl or roll it between your palms until clear. Never shake.
- Label and refrigerate at 2–8 °C.
Resulting concentration: 15 mg → 5 mg/mL · 20 mg → 6.67 mg/mL · 30 mg → 10 mg/mL · 40 mg → 13.33 mg/mL.
Storage: unreconstituted powder refrigerated (2–8 °C); reconstituted solution refrigerated and used within 28–30 days; do not freeze; protect from light and heat.
Draw volumes with 3 ml bacteriostatic water
| Vial | Concentration | 2 mg | 4 mg | 8 mg | 12 mg |
|---|---|---|---|---|---|
| 15 mg | 5 mg/mL | 40 u | 80 u | 160 u* | 240 u* |
| 20 mg | 6.67 mg/mL | 30 u | 60 u | 120 u* | 180 u* |
| 30 mg | 10 mg/mL | 20 u | 40 u | 80 u | 120 u* |
| 40 mg | 13.33 mg/mL | 15 u | 30 u | 60 u | 90 u |
* Exceeds the 100-unit (1 mL) capacity of a standard insulin syringe — split into two injections, or draw with a 3 mL syringe.
Injection Guide
- Wash hands and prepare a clean workspace.
- Swab the vial stopper; air-dry 10–15 s.
- Draw your dose; tap out air bubbles. For >100 units, split into two draws.
- Choose the site — lower abdomen (2–3 in from navel), upper thigh, or back of upper arm. Rotate weekly.
- Clean the site with alcohol; air-dry.
- Inject into a pinched skin fold at 45°, plunger slow and steady.
- Dispose in a sharps container; never recap or reuse.
Timing: once weekly, same day each week, any time of day. Half-life ~6 days. Missed dose ≤1–2 days late: inject as soon as possible and resume schedule; >3 days late: skip and resume next scheduled day. Rotate injection sites to prevent lipodystrophy.
Stacking & Contraindicated Combinations
Do not combine Retatrutide with any other GLP-1 receptor agonist (Semaglutide, Liraglutide, Tirzepatide) — it already has full GLP-1 agonism built in, and adding another creates redundant receptor activation with severely increased adverse-effect risk. No clinical stacking data exists for Retatrutide with any other peptide or drug.
Safety, Side Effects & Contraindications
Safety data is limited to a single Phase 2 trial (338 participants, 48 weeks). Long-term and rare adverse events are unknown.
Gastrointestinal (most common, dose-dependent)
- Nausea — up to 45% at 12 mg; peaks during titration, improves over time.
- Diarrhea — up to 27%; usually mild to moderate.
- Vomiting — up to 22%; more likely if titration is skipped.
- Constipation — reported; increase fiber and water intake.
- Decreased appetite — common, expected effect.
Glucagon-specific concerns
- Blood glucose monitoring strongly recommended, especially for diabetics/pre-diabetics.
- Hepatic effects — baseline and periodic liver function tests (ALT, AST).
- Heart rate — monitor resting heart rate, especially early in treatment.
Expected contraindications
Personal/family history of medullary thyroid carcinoma or MEN2; history of pancreatitis; pregnancy and breastfeeding; type 1 diabetes; severe hepatic or renal impairment.
Recommended baseline labs
Fasting glucose and HbA1c; complete metabolic panel with liver function; lipid panel; thyroid panel; kidney function; lipase and amylase; resting heart rate and blood pressure.
Common Mistakes
- Starting at full target dose without titrating.
- Treating Retatrutide dosing like Semaglutide (it is a triple agonist with glucagon activity).
- Combining with another GLP-1 agonist.
- Not monitoring blood glucose.
- Ignoring reconstitution math at high doses (12 mg at 10 mg/mL = 120 units, exceeding a 1 mL syringe).
- Not getting baseline labs before starting.
Key Takeaways
- First triple receptor agonist (GLP-1 + GIP + Glucagon); Phase 2 results up to 24.2% weight loss at 48 weeks.
- Titration is essential: 2 → 4 → 8 → 12 mg over 12 weeks.
- Once-weekly subcutaneous injection, ~6-day half-life.
- Do not combine with other GLP-1 agonists. Blood glucose monitoring and baseline labs are recommended.
- Not FDA-approved — Phase 3 (TRIUMPH); approval not expected before late 2026–2027.
References
- Jastreboff AM, et al. “Triple-hormone-receptor agonist retatrutide for obesity — a Phase 2 trial.” N Engl J Med. 2023;389(6):514-526.
- Rosenstock J, et al. “Retatrutide for people with type 2 diabetes: a Phase 2 trial.” Lancet. 2023;402(10401):529-544.
- Nauck MA, et al. “GLP-1 receptor agonists in the treatment of type 2 diabetes — state-of-the-art.” Mol Metab. 2021;46:101102.
- Finan B, et al. “A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents.” Nat Med. 2015;21(1):27-36.
- ClinicalTrials.gov. TRIUMPH 1 (NCT05929066); TRIUMPH 2 (NCT05929079).
Educational reference compiled from PeptideWiki (peptidewiki.co). For research purposes only — not for human use.
Download & Related Resources
Shop Retatrutide: 15 mg · 20 mg · 30 mg · 40 mg
Prefer a pre-filled pen? See the click-based dosing guides for the Retatrutide Pen 15 mg, 20 mg, 30 mg and 40 mg.
