← All peptidesFat LossOnce-weekly subcutaneous protocol for GLP-1 / GIP / glucagon triple-receptor metabolic research.
Retatrutide (LY3437943) is a novel triple-agonist peptide targeting GLP-1, GIP, and glucagon receptors simultaneously, engineered with a fatty-acid moiety for an approximately 6 day half-life and once-weekly dosing. Phase 2 trials demonstrated up to 24% body weight reduction at 48 weeks and HbA1c reductions of 1.3 to 2.0% in type 2 diabetes patients. Not FDA-approved; available for research use only.
Get Retatrutide → code PROFITProtocol Overview
Concise summary of the regimen.
GoalSupport significant weight reduction and metabolic improvements through triple-receptor activation.
ScheduleWeekly subcutaneous injections for 12 to 48 weeks (clinical trials ranged 36 to 48 weeks).
Dose Range2 to 12 mg weekly with gradual 4-week titration steps.
Reconstitution1.0 mL per 10 mg vial (~10.0 mg/mL).
StorageLyophilized frozen at -20 °C; reconstituted refrigerated for up to 4 weeks.
Dosing & Reconstitution
| PHASE | WEEKLY DOSE | UNITS PER INJECTION | VIALS NEEDED |
|---|
| Weeks 1 to 4 | 2 mg | 20 units (0.20 mL) | 1 vial per dose |
| Weeks 5 to 8 | 4 mg | 40 units (0.40 mL) | 1 vial per dose |
| Weeks 9 to 12 | 6 mg | 60 units (0.60 mL) | 1 vial per dose |
| Weeks 13+ | 8 mg | 80 units (0.80 mL) | 1 vial per dose |
| PHASE | WEEKLY DOSE | UNITS PER INJECTION | VIALS NEEDED |
|---|
| Weeks 1 to 4 | 2 mg | 20 units (0.20 mL) | 1 vial per dose |
| Weeks 5 to 8 | 4 mg | 40 units (0.40 mL) | 1 vial per dose |
| Weeks 9 to 12 | 8 mg | 80 units (0.80 mL) | 1 vial per dose |
| Weeks 13+ | 12 mg | 120 units (1.20 mL) | 2 vials per dose |
Frequency: Inject once weekly subcutaneously. All doses at or under 10 mg can be drawn from one reconstituted
Reconstitution Steps
- Draw 1.0 mL bacteriostatic water with a sterile syringe.
- Inject slowly down the vial wall; avoid foaming.
- Gently swirl until dissolved (do not shake).
- Label with date and refrigerate at 2 to 8 °C, protected from light.
- Use within 4 weeks of reconstitution. At 10.0 mg/mL, 1 unit = 0.01 mL » 100 mcg on a U-100 insulin syringe.
Storage Instructions
Proper storage preserves peptide quality.
- Lyophilized: store at -20 °C or colder in dry, dark conditions; stable for up to 24 months.
- Reconstituted: refrigerate at 2 to 8 °C; use within 4 weeks.
- Allow vials to reach room temperature before opening to reduce condensation.
- For extended storage, aliquot reconstituted solution and freeze at -20 °C; thaw only once before use.
Supplies Needed
Plan based on a 12 to 24 week weekly protocol with gradual titration.
Peptide Vials (Retatrutide, 10 mg each):
- 12 weeks (Standard to 6 mg): 5 vials.
- 24 weeks (Standard to 8 mg): 15 vials.
- 12 weeks (Aggressive to 8 mg): 6 vials.
Insulin Syringes (U-100, 1 mL capacity):
- Per week: 1 to 2 syringes (higher doses require split injections).
- 12 weeks: 12 to 24 syringes. 24 weeks: 24 to 48 syringes.
Bacteriostatic Water (10 mL bottles):
- 12 weeks (5 vials): 1 bottle. 24 weeks (15 vials): 2 bottles.
Alcohol Swabs:
- 12 weeks: ~50 swabs (1 x 100-count box).
- 24 weeks: ~100 swabs (1 x 100-count box).
Important Notes
Practical considerations for consistency and safety.
- Use new sterile insulin syringes for each injection; dispose in a sharps container.
- Rotate injection sites (abdomen, thighs, upper arms) systematically to reduce local irritation and
lipohypertrophy.
- For doses above 10 mg with 1.0 mL reconstitution, prepare multiple vials to obtain the required volume.
- For volumes above 1.0 mL, split into 2 separate injections at different sites for better absorption.
- Inject slowly; wait a few seconds before withdrawing the needle to ensure full dose delivery.
- Document weekly dose, date, and injection sites to maintain consistency.
- Gradual titration is essential to minimize gastrointestinal side effects; never skip escalation steps.
How This Works
Retatrutide's unique mechanism stems from its triple-agonist design. By activating GLP-1 and GIP receptors, it enhances insulin secretion (when glucose is present) and suppresses appetite, similar to existing incretin therapies. Additionally, Retatrutide's glucagon receptor agonism raises metabolic rate and promotes energy expenditure, further amplifying fat burning and weight loss beyond GLP-1/GIP effects alone. The peptide is engineered with a fatty-acid moiety to extend its circulation time (half-life ~6 days), allowing for once-weekly dosing. The combined hormonal activation leads to reduced calorie intake, increased satiety, and enhanced lipid oxidation, yielding potent weight loss and glycemic control. Preclinical studies confirmed that adding glucagon activity helps counteract the body's adaptive slowing of metabolism during weight loss.
Benefits & Side Effects
Observations from Phase 2 human clinical trials.
- Exceptional weight loss: Patients with obesity (without diabetes) lost an average of 22 to 24% of body
weight at 48 weeks on 8 to 12 mg doses.
- Glycemic control: In type 2 diabetes patients, HbA1c dropped by 1.3 to 2.0% (from ~8.0% to ~6.0%)
with 4 to 12 mg doses; ~82% reached HbA1c at or below 6.5%.
- Cardiometabolic improvements: Reductions in blood pressure, LDL cholesterol, waist circumference,
and liver fat content (over 80% resolution of hepatic steatosis on high doses).
- Universal response: 100% of participants on 8 to 12 mg achieved at least 5% weight reduction.
- GI side effects: Most common adverse effects were mild to moderate nausea, vomiting, and diarrhea,
occurring primarily during dose escalation.
- Side effects were dose-dependent and transient; gradual titration (4-week intervals) significantly reduced
GI discomfort compared to rapid escalation.
- No severe hypoglycemia or serious treatment-related adverse events reported in trials.
- Safety profile comparable to GLP-1 agonists when properly titrated.
Lifestyle Factors
Complementary strategies for best outcomes.
- Maintain a balanced, protein-forward diet with adequate micronutrients to support lean mass during
weight loss.
- Combine resistance training (2 to 3 times weekly) with regular aerobic activity to preserve muscle and
enhance metabolic adaptations.
- Prioritize sleep (7 to 9 hours) and stress management to support adherence and hormonal balance.
- Stay well-hydrated and monitor for signs of dehydration, especially during GI side effects.
- Work with healthcare providers to monitor metabolic markers (HbA1c, lipids, liver function) throughout
the protocol.
Injection Technique
General subcutaneous guidance from clinical best-practice resources.
- Clean the vial stopper and injection site with alcohol; allow to dry completely.
- Pinch a skinfold; insert the needle at 45 to 90 degrees into subcutaneous tissue.
- Do not aspirate for subcutaneous injections; inject slowly and steadily.
- For volumes above 1.0 mL, split into 2 injections at different sites (e.g., left and right abdomen).
- Rotate sites systematically (abdomen preferred; also thighs, upper arms) to avoid lipohypertrophy.
- Wait a few seconds after injecting before withdrawing needle to ensure full dose delivery.
- Dispose of used syringes immediately in an FDA-approved sharps container.
References
Source citations for further reading.
- Rosenstock J, et al. Retatrutide for type 2 diabetes: Phase 2 trial results (The Lancet, 2023).
- Jastreboff AM, et al. Triple-hormone-receptor agonist Retatrutide for obesity: Phase 2 trial (NEJM, 2023).
- Coskun T, et al. LY3437943 (Retatrutide): discovery to clinical proof of concept (Cell Metabolism, 2022).
- Hamza M, et al. Triple agonism based therapies for obesity (Current Obesity Reports, 2025).
Educational and research reference only. Not medical advice. For research use only; not for human consumption.