Tesofensine vs Tirzepatide
Side-by-side comparison of key properties, dosing, and research.
Fat Loss & Metabolic
TesofensineGLP-1 / Weight Loss Agonists
Tirzepatide- 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.
- Tirzepatide is an FDA-approved dual GIP/GLP-1 receptor agonist that produces greater weight loss than semaglutide in head-to-head trials. SURMOUNT-1 trial showed average 21% body weight reduction at 72 weeks at the highest dose. Marketed as Mounjaro (diabetes) and Zepbound (obesity).
- Half-Life
- 8-10 days (exceptionally long; accumulates over weeks)
- ~5 days
- Admin Route
- Oral
- SubQ
- Research
- —
- —
- Typical Dose
- 0.25-0.5 mg per day
- 2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg
- Frequency
- Once daily
- Once weekly, subcutaneous
- 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
- Average 21% body weight reduction at highest dose (SURMOUNT-1)
- Superior to semaglutide in head-to-head SURPASS trials
- Dual GIP/GLP-1 mechanism for enhanced metabolic control
- Significant reduction in HbA1c for type 2 diabetes
- Improved cardiovascular risk markers
- Reduces visceral fat preferentially
- FDA-approved for T2DM (Mounjaro) and obesity (Zepbound)
- Weekly dosing
- Side Effects
- Elevated heart rate and blood pressure (sympathomimetic)
- Dry mouth
- Insomnia and sleep disturbances
- Nausea
- +4 more
- Nausea (most common during titration)
- Vomiting
- Diarrhea or constipation
- Abdominal pain
- +3 more
- Stacks With
- —
- —