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Humanin vs Retatrutide

A detailed comparison to help you understand the differences and choose the right peptide for your research goals.

Humanin

Humanin is a mitochondrial-derived peptide with potent cytoprotective effects. Discovered in 2001, it has shown promise in protecting against age-related diseases including Alzheimer's, cardiovascular disease, and diabetes.

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Retatrutide

Retatrutide (LY3437943) is a first-in-class triple agonist peptide targeting GIP, GLP-1, and glucagon receptors simultaneously. Developed by Eli Lilly, it is currently in Phase 3 clinical trials and has demonstrated the highest weight loss of any obesity medication to date — up to 28.7% body weight reduction at 48 weeks. The triple-receptor mechanism represents the next evolution beyond dual agonists like tirzepatide.

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Side-by-Side Comparison

AspectHumaninRetatrutide
MechanismBinds to IGFBP-3 and BAX, inhibiting apoptosis. Activates STAT3 signaling and enhances cellular survival under stress. Protects mitochondrial function and reduces oxidative stress.Retatrutide is a synthetic peptide that activates three incretin/metabolic hormone receptors: (1) GLP-1 receptor — appetite suppression, insulin secretion, delayed gastric emptying, (2) GIP receptor — enhanced insulin sensitivity, improved fat metabolism, (3) Glucagon receptor — increased energy expenditure, hepatic fat mobilization, thermogenesis. The glucagon receptor component is the key differentiator, adding an energy-expenditure mechanism absent from GLP-1 and dual GIP/GLP-1 agonists. The molecule uses a C20 fatty diacid for albumin binding, enabling once-weekly dosing.
Typical DosageResearch protocols vary widely. Studies have used doses from micrograms to milligrams depending on the analog and route. HNG (S14G-Humanin) is a more potent analog.Phase 2 trial doses: 0.5 mg, 4 mg, 8 mg, and 12 mg weekly. The 12 mg dose produced maximum weight loss (28.7%). Phase 3 trials are evaluating doses up to 12 mg. Dose escalation schedule similar to other GLP-1s (start low, increase every 4 weeks). Final approved dosing not yet established — Phase 3 trials ongoing.
AdministrationSubcutaneous or intraperitoneal injection in research. Various analogs exist with different potencies and stabilities.Subcutaneous injection, once weekly. Phase 3 trials use pre-filled single-dose pens. Not yet commercially available — estimated FDA approval ~2027-2028.
Side EffectsLimited human data. Generally well-tolerated in animal studies. May affect glucose metabolism.Phase 2 data: nausea (up to 25%), diarrhea (up to 22%), vomiting (up to 15%), constipation, decreased appetite. GI side effects were dose-dependent and generally mild-to-moderate. Lower rates of nausea compared to semaglutide, potentially due to GIP component. Increased heart rate observed at higher doses.
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Key Differences

Detailed Analysis

Commonalities

Humanin and Retatrutide are used for different purposes and have limited overlap in their applications.

Which Should You Choose?

Choose Humanin for Cognitive Performance, Anti-Aging & Longevity. Choose Retatrutide for Fat Loss.

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