Cagrilintide vs PE-22-28
Side-by-side comparison of key properties, dosing, and research.
GLP-1 / Weight Loss Agonists
CagrilintideCognitive Enhancement
PE-22-28- Summary
- Cagrilintide is a long-acting amylin analog developed by Novo Nordisk. Amylin is a peptide hormone co-secreted with insulin from pancreatic beta cells. Cagrilintide slows gastric emptying, suppresses glucagon, and reduces appetite via central amylin receptors. In combination with semaglutide (CagriSema), Phase 2 trials achieved approximately 15% body weight reduction. Phase 3 trials (REDEFINE program) are ongoing.
- 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
- ~7–10 days
- Relatively short; CNS effects may persist due to neurogenic mechanisms
- Admin Route
- SubQ
- SubQ, Intranasal
- Research
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- Typical Dose
- 0.16 mg → 0.3 mg → 0.6 mg → 1.2 mg → 2.4 mg
- 200–400 mcg
- Frequency
- Once weekly
- Once daily
- Key Benefits
- ~15% body weight reduction in combination with semaglutide (CagriSema Phase 2)
- Synergistic appetite suppression complementing GLP-1 receptor agonists
- Reduces post-meal glucagon excursions improving glycemic control
- Slows gastric emptying contributing to prolonged satiety
- Once-weekly dosing via subcutaneous injection
- Potential for greater weight loss than semaglutide monotherapy
- 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, especially during titration)
- Vomiting
- Decreased appetite
- Diarrhea
- +2 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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