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 (60 mg Vial)
- Vial
- 60 mg Retatrutide
- Add diluent
- 3 mL
- Concentration
- 20 mg/mL
- 1 unit (U-100)
- 200 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 | 10 units | 0.1 mL |
| Weeks 5 to 8 | 4 mg | 20 units | 0.2 mL |
| Weeks 9 to 12 | 8 mg | 40 units | 0.4 mL |
| Weeks 13+ | 12 mg | 60 units | 0.6 mL |
Phase 3 Trial Schedule
| Study Phase | Weekly Dose | U-100 Units | Volume |
|---|---|---|---|
| Weeks 1 to 4 | 2 mg | 10 units | 0.1 mL |
| Weeks 5 to 8 | 4 mg | 20 units | 0.2 mL |
| Weeks 9 to 12 | 6 mg | 30 units | 0.3 mL |
| Weeks 13 to 16 | 9 mg | 45 units | 0.45 mL |
| Weeks 17+ | 12 mg | 60 units | 0.6 mL |
How to mix
- Clean the vial stopper and gather the sterile supplies required by the research procedure.
- Add 3 mL bacteriostatic water slowly down the vial wall.
- Gently swirl or roll until dissolved. Do not shake.
- Label the vial 20 mg/mL with the preparation date and follow the documented refrigerated storage period.
Dosing details
- The cited trials used once-weekly subcutaneous administration with separate target-dose designs. Their dosing schedule began with a lower starting dose and planned dose increases rather than starting at the assigned target.
- Phase 2 obesity study: The 48-week trial evaluated 1 mg, 4 mg, 8 mg, and 12 mg target groups; the lower-start 12 mg arm progressed from 2 mg to 4 mg, 8 mg, and 12 mg.
- Phase 2 diabetes study: Once-weekly retatrutide was evaluated across several target groups in adults with type 2 diabetes.
- Phase 3 design: Published program methods describe 4 mg, 9 mg, and 12 mg targets reached through four-week escalation stages.
- Phase 3 evidence: TRANSCEND-T2D-1 reported efficacy and safety findings for once-weekly retatrutide in adults with type 2 diabetes.
- Evidence boundary: These are study schedules and arithmetic conversions, not individualized dosing instructions.
Storage
- Document concentration, preparation, storage conditions, and every administration so the 60 mg calculations remain traceable.
- Preparation record: Label the vial 20 mg/mL and record the preparation date and exact diluent used.
- Storage record: Follow the supplied formulation and diluent instructions for temperature, light protection, and discard limits.
- Administration record: Log the study week, mass, U-100 units, mL, site, and observer initials.
- Agitation: Avoid shaking and unnecessary freeze-thaw exposure; protein and peptide stability depends on formulation-specific conditions.
- Sterile technique: Use a new sterile syringe and needle for every administration and place used sharps directly into an appropriate container.
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