Tesofensine vs Semaglutide
Side-by-side comparison of key properties, dosing, and research.
Fat Loss & Metabolic
TesofensineGLP-1 / Weight Loss Agonists
Semaglutide- 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.
- Semaglutide is an FDA-approved GLP-1 receptor agonist originally developed for type 2 diabetes that has proven remarkably effective for weight loss. Clinical trials show average 15–20% body weight reduction. It is marketed as Ozempic (diabetes) and Wegovy (weight management).
- Half-Life
- 8-10 days (exceptionally long; accumulates over weeks)
- ~7 days
- Admin Route
- Oral
- SubQ, Oral
- Research
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- Typical Dose
- 0.25-0.5 mg per day
- 0.25 mg → 0.5 mg → 1 mg → 1.7 mg → 2.4 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 15–20% body weight reduction in clinical trials (STEP trials)
- Significant reduction in appetite and food cravings
- Improvement in blood sugar control and insulin sensitivity
- Reduces cardiovascular risk (SELECT trial: 20% reduction in MACE)
- May reduce risk of kidney disease
- Improves metabolic markers (cholesterol, blood pressure)
- FDA-approved — extensively studied with robust safety data
- Weekly dosing convenience
- Side Effects
- Elevated heart rate and blood pressure (sympathomimetic)
- Dry mouth
- Insomnia and sleep disturbances
- Nausea
- +4 more
- Nausea (most common, especially during titration)
- Vomiting
- Diarrhea or constipation
- Abdominal discomfort
- +4 more
- Stacks With
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