Research & Educational Use Only. This protocol guide is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before beginning any research protocol.
Weight Loss / Appetite Suppression StackEvidence Grade: B (Tesofensine) / A (Semaglutide)
Tesofensine + Semaglutide Stack Protocol Guide
The Tesofensine + Semaglutide stack combines two of the most potent appetite-suppressing compounds available. Tesofensine is a triple monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine) originally developed for neurodegenerative diseases that demonstrated remarkable weight loss in clinical trials. Semaglutide, a GLP-1 receptor agonist, suppresses appetite through central and peripheral mechanisms. Together they attack appetite through completely different neurotransmitter systems: tesofensine via monoaminergic pathways and semaglutide via incretin signaling. This dual approach may overcome appetite adaptation that occurs with single-agent therapy.
Tesofensine inhibits reuptake of serotonin, norepinephrine, and dopamine in hypothalamic appetite centers. In Phase II trials, it produced 10-13% body weight loss at 0.5mg, outperforming most weight loss drugs. It also increases thermogenesis and fat oxidation. The dopaminergic component reduces food reward-seeking behavior.
Semaglutide Synergy
Semaglutide suppresses appetite through an entirely different pathway: GLP-1 receptor activation in the brain and gut. This complementary mechanism means that where one compound may lose effectiveness over time (receptor adaptation), the other continues working. The combination addresses both the hormonal and neurotransmitter components of appetite regulation.
Combined Dosing Protocol
Protocol
Compound 1
Compound 2
Timing
Duration
Conservative
Teso 0.25mg/day oral
Sema 0.25-0.5mg/wk
AM + weekly
12 weeks
Standard
Teso 0.5mg/day oral
Sema 1mg/wk
AM + weekly
12-16 weeks
Advanced
Teso 0.5mg/day oral
Sema 2.4mg/wk
AM + weekly
16 weeks
Reconstitution & Preparation
Tesofensine Preparation
Oral capsules: typically 0.25mg or 0.5mg
Take once daily in the morning
No reconstitution needed
Store at room temperature
Semaglutide Preparation
Pre-filled pens or lyophilized vials
If lyophilized: reconstitute per instructions
Store refrigerated 2-8°C
Weekly subcutaneous injection
Stacking Schedule (AM/PM Timing)
AM Protocol
7:00 AM: Tesofensine 0.5mg oral with water
Take on empty stomach or with light breakfast
Semaglutide: once weekly injection (consistent day)
PM Protocol
No PM dosing required
Avoid stimulants (caffeine) in afternoon/evening
Tesofensine may affect sleep; take early in day
Monitor heart rate and blood pressure regularly
Expected Timeline
Week 1-2
Start tesofensine at 0.25mg with semaglutide at 0.25mg/wk. Appetite noticeably reduced. Possible mild stimulant effects.
Week 3-4
Increase tesofensine to 0.5mg. Semaglutide at 0.5mg. Significant appetite suppression. Early weight loss 4-6 lbs.
Week 5-8
Full dual appetite suppression. Semaglutide at 1mg. Body composition changes visible. 8-15 lbs loss typical.
Week 9-16
Peak synergy. Continued semaglutide titration. Tesofensine thermogenic effects compound. Total loss 18-30 lbs.
Side Effects & Monitoring
Common Side Effects
Dry mouth (tesofensine, very common)
Insomnia or restlessness (tesofensine)
Elevated heart rate (tesofensine, dose-dependent)
Nausea (semaglutide, during titration)
Constipation
Precautions
Monitor blood pressure and heart rate weekly
Do not combine with other stimulants or MAOIs
Cardiovascular disease - use with extreme caution
MTC family history - semaglutide contraindication
Not suitable for those with anxiety disorders
Blood Work Recommendations
Panel
Markers
Timing
Cardiovascular
Resting HR, blood pressure
Weekly for first month, then biweekly
Metabolic
Fasting glucose, HbA1c
Baseline, Week 8, Week 16
Liver
ALT, AST, GGT
Baseline, Week 8
Thyroid
TSH, free T4
Baseline, Week 12
Cardiovascular monitoring is critical. Tesofensine can increase heart rate 5-10 bpm. Discontinue if resting HR exceeds 100 bpm consistently.
