PE-22-28 vs Retatrutide
Side-by-side comparison of key properties, dosing, and research.
Cognitive Enhancement
PE-22-28GLP-1 / Weight Loss Agonists
Retatrutide- Summary
- PE-22-28 is a synthetic analog of spadin derived from sortilin, designed to block TREK-1 potassium channels with rapid-onset antidepressant and neurogenic effects. It shows fast-acting depression relief (within 24 hours) and promotes hippocampal neurogenesis.
- Retatrutide is an investigational triple receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. Phase 2 trials showed an unprecedented average 24% body weight reduction at 48 weeks — exceeding any approved medication to date. It is in Phase 3 trials as of 2024.
- Half-Life
- Relatively short; CNS effects may persist due to neurogenic mechanisms
- ~10–12 days
- Admin Route
- SubQ, Intranasal
- SubQ
- Research
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- Typical Dose
- 200–400 mcg
- 0.5 mg → 1 mg → 2 mg → 4 mg → 8 mg → 12 mg
- Frequency
- Once daily
- Once weekly
- Key Benefits
- Rapid-onset antidepressant effects (within 24 hours)
- Promotes hippocampal neurogenesis
- Improves cognitive performance and memory
- Reduces anxiety and depressive behavior
- Novel mechanism — does not act on serotonin/dopamine/GABA receptors directly
- May help treatment-resistant depression
- Neuroprotective effects
- ~24% body weight reduction at 48 weeks in Phase 2 (highest dose)
- Superior to both semaglutide and tirzepatide in early trial comparisons
- Triple receptor mechanism addresses multiple obesity pathways
- Significant reduction in liver fat (MASH/NAFLD indication being studied)
- Improved cardiovascular and metabolic markers
- Once-weekly dosing
- Potential for greatest weight loss of any currently investigated compound
- Side Effects
- Generally well tolerated in animal models
- Limited human data available
- Possible mild headache or transient mood changes at initiation
- Injection site reactions (SC)
- Nausea and vomiting (common during titration, similar to semaglutide/tirzepatide)
- Diarrhea
- Constipation
- Heart rate increase (from glucagon receptor agonism)
- +2 more
- Stacks With
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