FOXO4-DRI vs Survodutide
Side-by-side comparison of key properties, dosing, and research.
Anti-Aging & Longevity
FOXO4-DRIGLP-1 / Weight Loss Agonists
Survodutide- 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.
- Survodutide is a once-weekly GLP-1/glucagon dual receptor agonist developed by Boehringer Ingelheim and Zealand Pharma. Phase 2 trials demonstrated up to 18.7% body weight reduction at 46 weeks, among the highest reported for a dual agonist. It is being studied for obesity and MASH (metabolic dysfunction-associated steatohepatitis), where the glucagon component drives hepatic fat clearance.
- Half-Life
- Estimated 2-4 hours (D-amino acid confers resistance to proteolysis)
- ~7 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
- 0.6 mg → 2.4 mg → 4.8 mg → 6 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
- Up to 18.7% body weight reduction at 46 weeks (Phase 2)
- Strong MASH activity — Phase 3 SYNCHRONIZE-NASH trials ongoing
- Reduces hepatic fat content via glucagon receptor-driven liver oxidation
- Once-weekly subcutaneous injection
- Greater weight loss potential than GLP-1 monotherapy
- Improvements in liver fibrosis markers in early data
- 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 (most common during titration)
- Vomiting
- Diarrhea
- Decreased appetite
- +3 more
- Stacks With
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