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The most potent oral fat-loss agent currently available. Triple reuptake inhibition for metabolic optimization.
Use this interactive flowchart to identify your metabolic goal and get a personalized protocol recommendation.
Identify your primary metabolic challenge and get a customized protocol recommendation
Select the metabolic challenge you want to address
Most diet pills just cut the wire to the "Hungry" light. Your body eventually adapts and finds other ways to make you eat.
Suppress appetite temporarily, but your metabolism slows down to compensate. You feel tired, cold, and eventually the cravings win.
Turns down the hunger dial AND keeps the metabolic furnace burning hot. You're not hungry, but you still have energy to burn fat.
The Analogy: If your metabolism is a thermostat, Tesofensine doesn't just lower the "eat" setting—it also prevents the "conserve energy" mode from kicking in.
Reduces "food noise" and emotional eating. You no longer think about food constantly.
Maintains metabolic rate during caloric deficit. Prevents adaptive thermogenesis.
Enhances fullness signals and prevents mood crashes during dieting.
Result: "Happy, Energetic, Not Hungry" – The perfect state for sustained fat loss.
| Phase | Dose | Duration | Notes |
|---|---|---|---|
| Titration | 250mcg daily | 7-14 days | Assess tolerance, especially sleep quality |
| Standard | 500mcg daily | 12-24 weeks | Full therapeutic dose; most weight loss occurs here |
| Conservative | 250mcg daily | Ongoing | For sensitive individuals or long-term maintenance |
| EOD Protocol | 500mcg EOD | As needed | For those with sleep issues (long half-life provides coverage) |
Understanding the long half-life (~9 days) and reaching steady state concentrations
Days 1-7
Peptide concentrations building in system. First dose effects may be felt within hours, but full accumulation begins.
Days 8-14
Concentrations reaching 50-75% of steady state. Effects becoming more consistent and predictable.
Days 15-21
Full steady state reached (~95% of maximum concentration). Peak therapeutic effects. Safe time to assess efficacy.
Week 4+
Sustained steady state. Long-term effects visible. Can assess weight loss progress and consider dose optimization.
Compare to Phentermine (DAT/NET only) or Bupropion (weak DAT/NET). Tesofensine has significantly stronger binding across all three systems.
9-day half-life creates "built-in tapering" when discontinuing. Unlike Phentermine (short half-life, rebound hunger), Tesofensine gradually wears off, reducing likelihood of weight regain.
By maintaining noradrenergic tone, Tesofensine prevents the typical 10-15% drop in resting metabolic rate seen during prolonged caloric restriction. This is the key differentiator from appetite-only suppressants.
Phase 2 trials complete; Phase 3 for obesity abandoned, now pursued for Prader-Willi Syndrome.
Most common side effect (20-30%)
The norepinephrine increase can disrupt sleep architecture.
Expected sympathetic effect
Resting HR may increase 5-10 bpm. Concern if >100 bpm.
Sympathetic activation sign
Decreased salivation from adrenergic effect. Usually improves over time.
More common in anxiety-prone individuals
Catecholamine increase can trigger anxiety in susceptible individuals.
42yo Female, stuck at 180lbs, "food noise"
Multiple failed diets, constant hunger thoughts, metabolic adaptation from years of yo-yo dieting.
250mcg daily × 2 weeks, then 500mcg daily × 10 weeks
38yo Male, desk job, pre-diabetic
HbA1c 6.3%, BMI 31, sedentary lifestyle, failed with GLP-1 (nausea).
Tesofensine 500mcg daily + structured exercise program
NO. Stacking with Adderall, Ritalin, or Vyvanse creates dangerous catecholamine excess that can cause hypertensive crisis or cardiac arrhythmias. Must discontinue ADHD meds before starting Tesofensine—consult your prescriber.
The 9-day half-life provides a natural taper, which reduces rebound hunger compared to short-acting stimulants. Studies show less weight regain than Phentermine. However, lifestyle habits during treatment determine long-term success.
Different mechanisms. GLP-1s work via gut hormones and slow gastric emptying (nausea common). Tesofensine works centrally via neurotransmitters (stimulant-like effects). Some patients who fail one approach succeed with the other.
Strongly discouraged. Alcohol affects all three neurotransmitter systems Tesofensine modulates. Expect amplified intoxication, worse hangovers, and potentially dangerous interactions. If you must drink, use extreme moderation.
With a 9-day half-life, missing one dose has minimal impact. Do not double up—simply continue with your next scheduled dose. This long half-life is why EOD dosing works for some patients.
Lower abuse potential than traditional stimulants (no euphoria at therapeutic doses). However, dopamine system involvement means caution in those with substance abuse history. Not recommended for patients with active addiction.
| Feature | Tesofensine | Semaglutide | Phentermine |
|---|---|---|---|
| Mechanism | Triple reuptake inhibitor | GLP-1 agonist | Amphetamine analogue |
| Weight Loss (24w) | 10-13% | ~15% | 5-7% |
| Energy Level | ↑ Increased | Neutral | ↑ Increased |
| Main Side Effects | Insomnia, HR↑, dry mouth | Nausea, vomiting, constipation | Insomnia, HR↑, tolerance |
| Rebound Weight | Lower (long t½) | Moderate | High |
| Route | Oral (daily) | Injectable (weekly) | Oral (daily) |
"GLP-1 agonists are arguably the most impactful drugs of the century, but if you lose muscle while on them, you are trading diabetes for frailty. Resistance training is not optional."
Metabolic health and muscle preservation
— Outlive (2023)"If you're on a GLP-1 agonist and not doing resistance training, you're trading metabolic health for frailty. Muscle loss on these drugs is real and preventable with proper training."
GLP-1 agonists and muscle preservation
— The Drive Podcast"The next generation of metabolic therapeutics will be triple agonists like Retatrutide. Combining GLP-1, GIP, and Glucagon activation addresses multiple pathways simultaneously—not just appetite suppression, but actual metabolic rate enhancement."
Future of metabolic therapeutics
— The Drive Podcast