PE-22-28 vs Retatrutide
A detailed comparison to help you understand the differences and choose the right peptide for your research goals.
PE-22-28
PE-22-28 is a synthetic peptide fragment derived from research on the SAMP8 mouse model of accelerated aging. It has shown potential for enhancing memory and reducing cognitive decline.
Full details →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.
Full details →Side-by-Side Comparison
| Aspect | PE-22-28 | Retatrutide |
|---|---|---|
| Mechanism | Derived from the protein that is deficient in SAMP8 mice. May work by inhibiting protein phosphatase 2A methylesterase, thereby affecting memory-related signaling pathways. | 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 Dosage | Research protocols vary. Intranasal dosing has been studied at various concentrations. Optimal human dosing not established. | 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. |
| Administration | Intranasal administration preferred for CNS delivery. Research compound with limited human use data. | Subcutaneous injection, once weekly. Phase 3 trials use pre-filled single-dose pens. Not yet commercially available — estimated FDA approval ~2027-2028. |
| Side Effects | Very limited human data. Primarily studied in animal models for safety and efficacy. | 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. |
| Best For |
Key Differences
Unique to PE-22-28:
Unique to Retatrutide:
Detailed Analysis
Commonalities
PE-22-28 and Retatrutide are used for different purposes and have limited overlap in their applications.
Which Should You Choose?
Choose PE-22-28 for Cognitive Performance, Anti-Aging & Longevity. Choose Retatrutide for Fat Loss.
Ready to Learn More?
Looking for trusted sources?