Retatrutide
Also known as: LY3437943
Triple GLP-1/GIP/Glucagon Agonist | Weight Loss & Diabetes
Overview
Novel triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors. Phase II trials demonstrated 24.2% weight loss at 48 weeks—the highest recorded for obesity medications.
Key benefits
- Superior weight loss (24.2% at 48 weeks)
- Improved glycemic control (HbA1c reduction up to 2.16%)
- Enhanced cardiovascular benefits
- Hepatic fat reduction (up to 82%)
- Triple mechanism addresses obesity through multiple pathways
Mechanism of action
Activates GLP-1 for appetite suppression, GIP for insulin sensitivity, and glucagon for increased energy expenditure and hepatic fat oxidation.
Molecular data
- Type
- Triple GLP-1/GIP/glucagon agonist
- Half-life
- ~6 days
Sequence
His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser
Indications
What the research community uses this compound for, with self-reported effectiveness.
Weight Loss
Superior Weight Reduction
Most effectiveClinical trials show 17.5% weight loss at 24 weeks and 24.2% at 48 weeks.
Sustained Weight Management
Most effectiveContinuous weight loss with no plateau at 48 weeks suggests greater long-term potential.
Triple Mechanism
Most effectiveAddresses obesity through appetite suppression, energy expenditure, and metabolic efficiency.
Type 2 Diabetes
Superior Glycemic Control
Most effectiveHbA1c reductions up to 2.16% with 82% achieving target levels below 6.5%.
Glucose-Dependent Regulation
EffectiveBalanced glycemic control with minimal hypoglycemia risk.
Insulin Sensitivity
EffectiveMarked improvements in sensitivity with potential for reduced exogenous insulin requirements.
Cardiovascular/Metabolic
Lipid Improvement
EffectiveNon-HDL cholesterol reductions up to 26.9%, triglyceride reductions up to 40.6%.
Blood Pressure Optimization
EffectiveConsistent decreases in systolic and diastolic blood pressure across trials.
Hepatic Fat Reduction
Most effectiveUp to 82% reduction in liver fat with normalization in 90% of participants.
Dosing protocols
Common protocols by delivery method. Adjust the curve below to model accumulation in your own cycle.
Injectable
Weekly subcutaneous injection into abdomen, thigh, or upper arm with site rotation.
| Protocol | Dose | Frequency | Route / duration |
|---|---|---|---|
| Starting Dose (Week 1-4) | 0.5mg | Once weekly | SubQ |
| Low Maintenance (Week 4-8) | 1mg | Once weekly | SubQ |
| Escalation (Week 8-12) | 2mg | Once weekly | SubQ |
| Moderate (Week 12-16) | 4mg | Once weekly | SubQ |
| Advanced (Week 16-20) | 8mg | Once weekly | SubQ |
| Maximum Efficacy (Week 20+) | 12mg | Once weekly | SubQ |
Preparation
You will need
- Sterile bacteriostatic water for injection
- Lyophilized Retatrutide vial
- Insulin syringes (0.3-1mL capacity)
- Alcohol swabs
- Sharps disposal container
Steps
- Allow vial to reach room temperature (15-20 minutes)
- Clean vial top with alcohol swab and air dry completely
- Add calculated bacteriostatic water slowly down vial side
- Gently swirl in circular motions—avoid vigorous shaking
- Allow full dissolution (2-3 minutes); solution should be clear and colorless
- Store reconstituted solution refrigerated at 2-8°C for up to 28 days
- Inject subcutaneously; rotate sites weekly
Work out the water volume and syringe units in the reconstitution calculator →
Interactions
Pairwise interactions with other compounds you might be cycling — the same data behind the cycle builder's safety check.
Tirzepatide
AvoidDo not combine with other dual/triple agonists—risk of severe hypoglycemia and excessive GI effects.
Semaglutide
AvoidDo not combine—overlapping GLP-1 agonist mechanisms increase severe hypoglycemia risk.
Cagrilintide
MonitorBoth cause significant GI effects. Not recommended without specialist supervision.
Insulin
MonitorMay significantly reduce insulin requirements. Monitor blood glucose and adjust insulin doses accordingly.
Oral Contraceptives
MonitorSpace oral contraceptives by 1 hour before retatrutide due to delayed gastric emptying.
Metformin
CompatibleSafe combination tested in clinical trials. Different mechanisms work complementarily for glucose control.
SGLT2 Inhibitors
CompatibleClinical trials included SGLT2 inhibitors with no safety concerns.
BPC-157
CompatibleSafe combination; BPC-157 may provide GI protective benefits during retatrutide use.
Timeline
Typical week-by-week effects reported in clinical and observational data.
- Week 1-2
Initial appetite suppression and mild GI effects as body adapts to triple hormone activation
- Week 2-4
Noticeable food cravings reduction and portion size decrease; early weight loss (2-5%)
- Week 4-8
Significant appetite control and steady weight loss (5-10%); improved glucose control
- Week 8-16
Substantial weight reduction (10-18%) with enhanced energy expenditure
- Week 16-24
Major weight loss milestone (15-22%) with cardiovascular benefits and liver fat reduction
- Week 24-48
Maximum clinical efficacy (20-24.2%) with comprehensive metabolic improvements
Safety
Reported adverse effects, contraindications, and what to monitor on cycle.
Common side effects
- Gastrointestinal effects (nausea, vomiting, diarrhea)—typically mild to moderate
- Heart rate increases—common especially in first 24 weeks
- Appetite suppression
- Mild dehydration
Stop signs — stop and seek advice
- Severe persistent nausea or vomiting preventing adequate nutrition
- Signs of pancreatitis: severe abdominal pain radiating to back
- Severe hypoglycemia symptoms: confusion, dizziness, sweating
- Excessive weight loss (>3 lbs per week consistently or >25% total body weight)
- Gallbladder problems: severe right upper abdominal pain
Contraindications
- Personal or family history of medullary thyroid carcinoma
- MEN2 syndrome
- Severe renal impairment
Monitoring
- Cardiovascular status (especially heart rate)
- Blood glucose if diabetic
- Weight loss rate
- Signs of pancreatitis
- Gastrointestinal tolerability
Quality checks
What a legitimate product looks like, what should give pause, and what should make you stop.
Good signs
- Pharmaceutical-grade white powder with uniform texture
- Proper cold chain maintenance (2-8°C refrigeration)
- Clear, colorless reconstituted solution without particles
- Stable extended half-life effects (consistent appetite suppression between doses)
Warning signs
- Source verification critical—counterfeit versions circulate due to investigational status
Stop signs — don't use
- Rapid tolerance or effectiveness loss suggests degraded or counterfeit product
- Unusual side effect profile may indicate contamination
Recent research
Newer papers and trial readouts on file for this compound, with source and date.
2025-10
TRIUMPH Phase 3 Program Design Published
Rationale and design of the four TRIUMPH registrational Phase 3 trials published, enrolling 5,800+ participants across obesity, sleep apnea, osteoarthritis, and cardiovascular disease populations. Results expected 2026.
2025-06
Body Composition Substudy Results
Phase 2 substudy published in Lancet Diabetes & Endocrinology showing retatrutide significantly reduces total body fat mass with fat mass reductions of up to 26.1% at the 8mg dose in people with type 2 diabetes.
2024-06
MASLD Phase 2a Results Published
Nature Medicine published data showing up to 82.4% liver fat reduction with retatrutide 12mg, with normalization of liver fat in 86% of participants at 24 weeks.
References
Primary literature and clinical-trial data informing this entry.
Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
Jastreboff, A.M., et al. · New England Journal of Medicine · 2023
Participants: 338 adults with obesity
Landmark phase 2 RCT showing dose-dependent weight loss: 24.2% at 48 weeks with 12mg dose — the highest recorded for any obesity medication at the time. Weight reduction of ≥15% achieved in 83% of 12mg recipients.
Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a phase 2 trial
Rosenstock, J., et al. · The Lancet · 2023
Participants: 281 adults with type 2 diabetes
Phase 2 trial in type 2 diabetes demonstrating clinically meaningful HbA1c reductions and robust weight loss of up to 16.9% at 36 weeks, with safety profile consistent with GLP-1 receptor agonists.
Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial
Sanyal, A.J., et al. · Nature Medicine · 2024
Participants: 98 participants with MASLD
Dose-dependent liver fat reduction: 82.4% at 12mg dose. Normal liver fat (<5%) achieved in 86% of 12mg recipients vs 0% placebo at 24 weeks. Improvements linked to changes in body weight, abdominal fat, and insulin sensitivity.
Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide
Li, W., et al. · Cell Discovery · 2024
Cryo-EM structures reveal how retatrutide simultaneously activates GLP-1R, GIPR, and GCGR through distinct receptor-binding modes, explaining the molecular basis for its triple agonist activity and superior clinical efficacy.
TRIUMPH registrational clinical trials: Rationale and design
Aronne, L.J., et al. · Obesity · 2025
Participants: 5,800+ participants across 4 trials
Phase 3 TRIUMPH program design: four multicenter, randomized, double-blind studies assessing weekly retatrutide for obesity, obstructive sleep apnea, knee osteoarthritis, and weight management in cardiovascular disease populations.
Effects of retatrutide on body composition in people with type 2 diabetes: a phase 2 substudy
Rosenstock, J., et al. · The Lancet Diabetes & Endocrinology · 2025
Substudy demonstrating significant total body fat mass reduction with retatrutide vs placebo and dulaglutide. Proportion of lean mass loss to total weight loss was similar to other obesity treatments.
Last updated . How this page was sourced is described in the methodology.