Dulaglutide vs PE-22-28
Side-by-side comparison of key properties, dosing, and research.
GLP-1 / Weight Loss Agonists
DulaglutideCognitive Enhancement
PE-22-28- Summary
- Dulaglutide (brand name Trulicity) is a once-weekly GLP-1 receptor agonist approved by the FDA for type 2 diabetes management and cardiovascular risk reduction. It consists of two GLP-1 analog chains fused to a modified IgG4 Fc fragment, extending its half-life to approximately 5 days. While primarily a diabetes medication, it produces meaningful weight loss and has established cardiovascular outcomes data from the REWIND trial.
- 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
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- Typical Dose
- 0.75 mg → 1.5 mg
- 200–400 mcg
- Frequency
- Once weekly
- Once daily
- Key Benefits
- FDA-approved for type 2 diabetes
- Once-weekly subcutaneous dosing via auto-injector pen
- Reduces HbA1c by approximately 1.1–1.6%
- Modest weight loss of 1.5–3 kg at approved doses
- Demonstrated cardiovascular risk reduction (REWIND trial)
- Established long-term safety profile
- Renal protective effects in CKD
- 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, typically transient)
- Diarrhea
- Vomiting
- Decreased appetite
- +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
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