Retatrutide
LY3437943 · Triple G · GGG Agonist
The next-gen triple agonist (GLP-1/GIP/Glucagon) that produced 24% weight loss in trials — making Semaglutide look modest.
What is Retatrutide?
If Semaglutide (Ozempic/Wegovy) changed the weight loss game, Retatrutide might break it entirely. This is Eli Lilly's triple receptor agonist — hitting GLP-1, GIP, and glucagon receptors simultaneously. In Phase 2 trials, participants lost up to 24% of body weight at 48 weeks. That is approaching bariatric surgery territory with an injection.
The glucagon receptor component is what distinguishes Retatrutide from Tirzepatide (which only hits GLP-1 and GIP). Glucagon increases energy expenditure, promotes fat oxidation, and reduces liver fat. Combined with the appetite suppression of GLP-1 and the insulinotropic effects of GIP, you get a metabolic triple threat that addresses weight from multiple angles simultaneously.
This is not yet approved — Phase 3 trials are ongoing — but the biohacking and weight loss communities are already sourcing research-grade Retatrutide. The results are preliminary but genuinely remarkable. If Phase 3 confirms Phase 2, this could become the most effective pharmaceutical weight loss agent ever developed.
How Does It Work?
Retatrutide activates three receptors simultaneously:
1. GLP-1 receptor: Reduces appetite, slows gastric emptying, improves insulin sensitivity, provides cardiovascular benefit. 2. GIP receptor: Enhances insulin secretion, may improve fat metabolism, reduces inflammation. Synergises with GLP-1 for greater appetite suppression than either alone. 3. Glucagon receptor: Increases hepatic energy expenditure, promotes fatty acid oxidation, reduces liver fat, increases thermogenesis. This is the novel addition that drives additional weight loss beyond dual agonists.
The triple mechanism means weight loss comes from reduced intake AND increased expenditure — a combination single-mechanism drugs cannot achieve.
What Does The Research Say?
Strong clinical evidence from human trials.
Phase 2 trial (2023, NEJM): 338 participants with obesity. 24.2% weight loss at highest dose (12mg) at 48 weeks. Dose-dependent response across all doses tested. Significantly more weight loss than Tirzepatide achieved at similar timepoints.
Phase 3 trials: Currently enrolling/ongoing for obesity and Type 2 diabetes indications. Results expected 2025-2026.
Liver: Dramatic reductions in liver fat content — potentially relevant for NAFLD/NASH.
Safety: GI side effects (nausea, diarrhoea) similar to other GLP-1 agonists. No unexpected safety signals in Phase 2.
Reported Dosages
These are dosages reported in research literature and community reports. They are NOT medical recommendations. Always consult a healthcare professional.
Clinical trial doses: 1mg, 4mg, 8mg, 12mg weekly subcutaneous injection (dose-escalation over 4-8 weeks).
Maximum efficacy seen at 12mg weekly.
Dose escalation is critical — starting at full dose causes severe GI side effects.
DISCLAIMER: NOT YET APPROVED. Currently in Phase 3 clinical trials. Any current use is with research-grade compounds of uncertain quality. Wait for approval or participate in a clinical trial. The GI side effects at full dose without proper escalation can be severe.
Side Effects & Risks
Nausea (most common — typically improves after 4-8 weeks), diarrhoea, vomiting, decreased appetite (intended effect), constipation. Similar GI profile to other GLP-1 agonists but potentially more pronounced due to triple mechanism.
Concerns shared with class: muscle loss alongside fat loss (protein intake and resistance training critical), potential thyroid C-cell effects (theoretical, based on animal data), pancreatitis risk (rare), gallbladder issues with rapid weight loss.
Legal Status by Country
Not approved. Available as research chemical only.
Not FDA-approved. Phase 3 trials ongoing (Eli Lilly). Research chemical availability.
Not EMA-approved. Clinical trials ongoing.
Not TGA-approved. Research chemical.
Important Disclaimer
This profile is for educational and research purposes only. It does not constitute medical advice. Retatrutide may be regulated or illegal in your jurisdiction. Do not use any compound without consulting a qualified healthcare professional. StackPedia does not sell, supply, or promote the use of any controlled substance.