Retatrutide
Also called LY3437943; "triple agonist"
An investigational once-weekly medicine from Eli Lilly that activates three hormone receptors: GIP, GLP-1 and glucagon. Phase 3 trials report substantial weight loss, but it is not FDA approved.
Overview
What it is
A single peptide molecule with triple-receptor activity. It is not a mixture of semaglutide and tirzepatide, and it is not a stronger version of Ozempic.
How it works
GLP-1 and GIP shape the body's response to food and blood sugar; glucagon signaling adds effects on energy use and the liver. More targets do not automatically mean a better treatment for every person.
What the research shows
A 2023 phase 2 trial in obesity showed large dose-related weight loss over 48 weeks. TRIUMPH-1 (adults with obesity, no diabetes) and TRIUMPH-2 (adults with type 2 diabetes) were published in September 2026; in TRIUMPH-2 the highest-dose group lost 18.8% on average (20.8% under the sponsor's efficacy analysis). TRIUMPH-1 also reported improvements in knee osteoarthritis and sleep apnea subgroups.
Studied for
- Obesity without diabetesphase 3
- Obesity with type 2 diabetesphase 3
- Knee osteoarthritis and sleep apneasubgroups
Safety and regulatory status
Safety and side effects
In TRIUMPH-2's highest-dose group, diarrhea occurred in 34% (13% placebo) and nausea in 28% (8% placebo). Low blood pressure (6% vs under 1%) and unusual skin sensations (7% vs 1%) were also reported. Heart rate rose in a dose-related way in phase 2, peaking around week 24.
Regulatory status
Not FDA approved as of October 2026. FDA says it cannot legally be used in compounding. Lilly plans a US submission in early 2027.
Mixing and dosing reference
Reference information only. Read before using this section.
Retatrutide Dosage Protocol (5 mg Vial)
- Vial
- 5 mg Retatrutide
- Add diluent
- 1 mL
- Concentration
- 5 mg/mL
- 1 unit (U-100)
- 50 mcg in 0.01 mL
- Route
- Subcutaneous
- How often
- Once weekly by subcutaneous administration in the cited human trials.
- Typical range
- The cited programs evaluated target amounts through 12 mg weekly.
Phase 2 Trial Schedule
| Study Phase | Weekly Dose | U-100 Units | Volume |
|---|---|---|---|
| Weeks 1 to 4 | 2 mg | 40 units | 0.4 mL |
| Weeks 5 to 8 | 4 mg | 80 units | 0.8 mL |
| Weeks 9 to 12 | 8 mg | 160 units | 1.6 mL |
| Weeks 13+ | 12 mg | 240 units | 2.4 mL |
Phase 3 Trial Schedule
| Study Phase | Weekly Dose | U-100 Units | Volume |
|---|---|---|---|
| Weeks 1 to 4 | 2 mg | 40 units | 0.4 mL |
| Weeks 5 to 8 | 4 mg | 80 units | 0.8 mL |
| Weeks 9 to 12 | 6 mg | 120 units | 1.2 mL |
| Weeks 13 to 16 | 9 mg | 180 units | 1.8 mL |
| Weeks 17+ | 12 mg | 240 units | 2.4 mL |
How to mix
- Clean the vial stopper and gather the sterile supplies required by the research procedure.
- Add 1 mL bacteriostatic water slowly down the vial wall.
- Gently swirl or roll until dissolved. Do not shake.
- Label the vial 5 mg/mL with the preparation date and follow the documented refrigerated storage period.
Dosing details
- Phase 2 lower-start 12 mg arm: 2 mg, 4 mg, 8 mg, then 12 mg in four-week stages.
- Phase 3 12 mg target: 2 mg, 4 mg, 6 mg, 9 mg, then 12 mg in four-week stages.
- Other target groups: The trials included lower assigned targets; not every participant escalated to 12 mg.
- Measurement: The primary chart keeps peptide mass, U-100 units, mL, and once-weekly frequency together.
- Strength consistency: Vial size changes concentration, vial yield, and supply totals; it does not change the assigned research amount.
Storage
- Before reconstitution: Keep the lyophilized vial dry, protected from light, and stored according to the exact product documentation.
- After reconstitution: Refrigerate only as the supplied formulation and diluent instructions permit.
- Label the vial: Record the 5 mg/mL concentration, reconstitution date, storage conditions, and documented discard date.
- Handling: Gently swirl or roll rather than shake the vial, and avoid unnecessary agitation or repeated freeze-thaw cycles because peptide stability is formulation-dependent.
Protocol source: PeptideDosages.com
Common questions
Is retatrutide the same as Ozempic?
No. Ozempic is semaglutide, a different molecule.
Is it better than tirzepatide?
No head-to-head trial exists; comparing numbers across separate trials is misleading.
Does the trial data mean online products are safe?
No. Trial results apply to the studied product, not products of unknown origin.
Related in Metabolic Health
Sources and further reading (5)
- TRIUMPH-1 phase 3 trial of retatrutide in obesity. NEJM, 2026.
- TRIUMPH-2 phase 3 trial in overweight or obesity with type 2 diabetes. Lancet, 2026.
- Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity: phase 2. NEJM, 2023.
- FDA. Concerns with unapproved GLP-1 drugs used for weight loss.
- Source summary: PeptideDosages.com research overview (rewritten for NVO).
Laboratory research material: GLP-3R (NVO research code) Research Use Only