Tesofensine vs FOXO4-DRI
Side-by-side comparison of key properties, dosing, and research.
Fat Loss & Metabolic
TesofensineAnti-Aging & Longevity
FOXO4-DRI- Summary
- Tesofensine is a triple monoamine reuptake inhibitor (TMRI) that blocks reuptake of serotonin, dopamine, and norepinephrine. Originally developed for Alzheimer's and Parkinson's disease, it was repurposed as a potent weight loss agent after clinical trials demonstrated substantial fat loss via appetite suppression and increased energy expenditure.
- 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.
- Half-Life
- 8-10 days (exceptionally long; accumulates over weeks)
- Estimated 2-4 hours (D-amino acid confers resistance to proteolysis)
- Admin Route
- Oral
- Subcutaneous, Intraperitoneal (research)
- Research
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- Typical Dose
- 0.25-0.5 mg per day
- 5 mg/kg in rodent studies; human equivalent approximately 0.5-1 mg/kg
- Frequency
- Once daily
- 3 consecutive days per cycle
- Key Benefits
- Potent appetite suppression via triple monoamine reuptake inhibition
- Significant weight loss (8-12% body weight in phase II trials at 0.5 mg)
- Increases basal metabolic rate and energy expenditure
- Reduces fat mass preferentially over lean mass
- Potential cognitive benefit via dopaminergic and noradrenergic enhancement
- Longer half-life than sibutramine allows once-daily dosing
- 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
- Side Effects
- Elevated heart rate and blood pressure (sympathomimetic)
- Dry mouth
- Insomnia and sleep disturbances
- Nausea
- +4 more
- 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
- Stacks With
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