Semaglutide vs PE-22-28
Side-by-side comparison of key properties, dosing, and research.
GLP-1 / Weight Loss Agonists
SemaglutideCognitive Enhancement
PE-22-28- Summary
- Semaglutide is an FDA-approved GLP-1 receptor agonist originally developed for type 2 diabetes that has proven remarkably effective for weight loss. Clinical trials show average 15–20% body weight reduction. It is marketed as Ozempic (diabetes) and Wegovy (weight management).
- 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 days
- Relatively short; CNS effects may persist due to neurogenic mechanisms
- Admin Route
- SubQ, Oral
- SubQ, Intranasal
- Research
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- Typical Dose
- 0.25 mg → 0.5 mg → 1 mg → 1.7 mg → 2.4 mg
- 200–400 mcg
- Frequency
- Once weekly, subcutaneous
- Once daily
- Key Benefits
- Average 15–20% body weight reduction in clinical trials (STEP trials)
- Significant reduction in appetite and food cravings
- Improvement in blood sugar control and insulin sensitivity
- Reduces cardiovascular risk (SELECT trial: 20% reduction in MACE)
- May reduce risk of kidney disease
- Improves metabolic markers (cholesterol, blood pressure)
- FDA-approved — extensively studied with robust safety data
- Weekly dosing convenience
- 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
- Diarrhea or constipation
- Abdominal discomfort
- +4 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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