Tesofensine Protocol Guide
Tesofensine is a triple monoamine reuptake inhibitor that blocks the reuptake of serotonin, norepinephrine, and dopamine. Originally developed for Alzheimer's and Parkinson's disease, Phase 2 clinical trials revealed remarkable weight loss efficacy -- subjects receiving 0.5mg daily lost approximately 12.8% of body weight over 24 weeks, roughly double the effect of currently approved anti-obesity medications at that time. Tesofensine suppresses appetite, increases satiety signaling, modestly increases resting energy expenditure, and improves mood and motivation through dopaminergic enhancement. This protocol covers oral dosing at 0.25-0.5mg daily, cardiovascular monitoring requirements, tapering strategies, and metabolic stacking options.
Protocol Overview
- Compound
- Tesofensine
- Category
- Weight Loss / Appetite Suppression
- Mechanism
- Triple monoamine reuptake inhibitor (5-HT, NE, DA); suppresses appetite, increases satiety, modestly raises metabolic rate
- Molecular Weight
- 426.97 g/mol
- Half-Life
- ~220 hours (8-9 days)
- Form
- Oral capsules (0.25mg, 0.5mg)
- Route
- Oral
- Frequency
- 1x daily (morning)
- Cycle Length
- 12-24 weeks, taper off over 1-2 weeks
Dosing Protocol
| Protocol | Dose | Frequency | Route | Duration |
|---|---|---|---|---|
| Introductory | 0.25 mg | 1x daily (AM) | Oral | 2 weeks |
| Standard | 0.5 mg | 1x daily (AM) | Oral | 12-24 weeks |
| Conservative | 0.25 mg | 1x daily (AM) | Oral | 12-24 weeks |
Key principle: The very long half-life (~8-9 days) means steady-state takes 6-8 weeks to achieve. Do not increase dose prematurely. Morning dosing is preferred to minimize insomnia risk. Always taper off gradually rather than abrupt cessation.
Administration Guide
Oral Administration
- Form: Capsules (no reconstitution needed)
- Timing: Morning, with or without food
- Consistency: Take at same time daily
- Do not: Double doses if missed; resume next day
- Taper: Reduce to 0.25mg for 2 weeks before stopping
Cardiovascular Monitoring
- Heart rate: Monitor weekly; expect +7-8 bpm increase
- Blood pressure: Check 2x weekly initially
- Alert threshold: Sustained HR >100 bpm or BP >140/90
- ECG: Baseline and at week 4 recommended
Expected Timeline
Side Effects & Monitoring
Common Side Effects
- Dry mouth (most common)
- Insomnia or sleep disturbance
- Constipation
- Increased heart rate (+7-8 bpm average)
- Mild nausea (usually transient)
- Headache
Most side effects are dose-dependent and more pronounced at 1.0mg (which is not recommended).
Serious Precautions
- Contraindicated with uncontrolled hypertension
- Do not combine with MAOIs or SSRIs (serotonin syndrome risk)
- Avoid in subjects with cardiovascular disease or arrhythmias
- Monitor for mood changes, anxiety, or agitation
- Not approved by FDA; investigational compound
- Taper off gradually to avoid withdrawal effects
Stacking Recommendations
Compatible Compounds
- 5-Amino-1MQ: NNMT inhibition for complementary fat metabolism
- AOD-9604: GH fragment for additional fat loss without stimulant effects
- BPC-157: Gut health and neuroprotection support
- L-Carnitine: Fatty acid transport enhancement
Avoid Combining With
- SSRIs/SNRIs: Serotonin syndrome risk
- MAOIs: Dangerous hypertensive crisis potential
- Stimulants: Additive cardiovascular strain
- Other appetite suppressants: Excessive catecholaminergic activity
Blood Work Recommendations
| Panel | Markers | Timing |
|---|---|---|
| Cardiovascular | ECG, heart rate, blood pressure | Baseline, Week 4, Week 12, Week 24 |
| Metabolic Panel | Fasting glucose, insulin, HbA1c, lipid panel | Baseline, Week 12, Week 24 |
| Liver Function | ALT, AST, GGT, bilirubin | Baseline, Week 12 |
| Body Composition | DEXA scan, waist circumference | Baseline, Week 12, Week 24 |
Cardiovascular monitoring is the most critical component. ECG at baseline rules out pre-existing conduction abnormalities. Track metabolic improvements to quantify benefits alongside weight loss.
Related Tools & Resources
