FOXO4-DRI vs Retatrutide
Side-by-side comparison of key properties, dosing, and research.
Anti-Aging & Longevity
FOXO4-DRIGLP-1 / Weight Loss Agonists
Retatrutide- Summary
- FOXO4-DRI is a D-retro-inverso peptide derived from the FOXO4 protein that selectively induces apoptosis in senescent cells. By disrupting the FOXO4-p53 interaction that keeps senescent cells alive, it triggers programmed cell death specifically in these aging, pro-inflammatory cells while sparing healthy tissue.
- 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
- Estimated 2-4 hours (D-amino acid confers resistance to proteolysis)
- ~10–12 days
- Admin Route
- Subcutaneous, Intraperitoneal (research)
- SubQ
- Research
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- Typical Dose
- 5 mg/kg in rodent studies; human equivalent approximately 0.5-1 mg/kg
- 0.5 mg → 1 mg → 2 mg → 4 mg → 8 mg → 12 mg
- Frequency
- 3 consecutive days per cycle
- Once weekly
- Key Benefits
- Selectively clears senescent cells (senolytics)
- Reduces senescence-associated secretory phenotype (SASP) and chronic inflammation
- Demonstrated restoration of physical fitness in aged mice
- May improve healthspan and reduce age-related tissue dysfunction
- Potential for treatment of age-related pathologies driven by cellular senescence
- Does not affect healthy non-senescent cells at therapeutic doses
- ~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
- Limited human data; largely preclinical evidence
- Possible temporary inflammatory response as senescent cells are cleared (senolytic effect)
- Weight loss observed at high doses in rodent studies
- Unknown long-term safety profile in humans
- 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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