Retatrutide vs Tesofensine
Side-by-side comparison of key properties, dosing, and research.
GLP-1 / Weight Loss Agonists
RetatrutideFat Loss & Metabolic
Tesofensine- Summary
- 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.
- 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.
- Half-Life
- ~10–12 days
- 8-10 days (exceptionally long; accumulates over weeks)
- Admin Route
- SubQ
- Oral
- Research
- —
- —
- Typical Dose
- 0.5 mg → 1 mg → 2 mg → 4 mg → 8 mg → 12 mg
- 0.25-0.5 mg per day
- Frequency
- Once weekly
- Once daily
- Key Benefits
- ~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
- 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
- Side Effects
- Nausea and vomiting (common during titration, similar to semaglutide/tirzepatide)
- Diarrhea
- Constipation
- Heart rate increase (from glucagon receptor agonism)
- +2 more
- Elevated heart rate and blood pressure (sympathomimetic)
- Dry mouth
- Insomnia and sleep disturbances
- Nausea
- +4 more
- Stacks With
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