Tirzepatide vs PE-22-28
Side-by-side comparison of key properties, dosing, and research.
GLP-1 / Weight Loss Agonists
TirzepatideCognitive Enhancement
PE-22-28- Summary
- Tirzepatide is an FDA-approved dual GIP/GLP-1 receptor agonist that produces greater weight loss than semaglutide in head-to-head trials. SURMOUNT-1 trial showed average 21% body weight reduction at 72 weeks at the highest dose. Marketed as Mounjaro (diabetes) and Zepbound (obesity).
- 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.
- Half-Life
- ~5 days
- Relatively short; CNS effects may persist due to neurogenic mechanisms
- Admin Route
- SubQ
- SubQ, Intranasal
- Research
- —
- —
- Typical Dose
- 2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg
- 200–400 mcg
- Frequency
- Once weekly, subcutaneous
- Once daily
- Key Benefits
- Average 21% body weight reduction at highest dose (SURMOUNT-1)
- Superior to semaglutide in head-to-head SURPASS trials
- Dual GIP/GLP-1 mechanism for enhanced metabolic control
- Significant reduction in HbA1c for type 2 diabetes
- Improved cardiovascular risk markers
- Reduces visceral fat preferentially
- FDA-approved for T2DM (Mounjaro) and obesity (Zepbound)
- Weekly dosing
- 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
- Side Effects
- Nausea (most common during titration)
- Vomiting
- Diarrhea or constipation
- Abdominal pain
- +3 more
- Generally well tolerated in animal models
- Limited human data available
- Possible mild headache or transient mood changes at initiation
- Injection site reactions (SC)
- Stacks With
- —
- —