Tesofensine is the odd one out in this category. It is not a peptide — not a hormone analogue — and has nothing to do with GLP-1. It is a small molecule that blocks the reuptake of noradrenaline, dopamine and serotonin. Pharmacologically it is closer to a stimulant than to anything else on this site.
It was originally developed for Parkinson's disease and Alzheimer's, failed at both, and the weight loss seen incidentally in those trials is why it is still discussed. Phase 2 trials in obesity reported roughly 10% weight loss over 24 weeks, which was striking at the time.
It has never been approved in the United States or Europe. The mechanism is the reason: drugs that raise all three monoamines have a long and unhappy history in obesity medicine. Sibutramine reached market and was withdrawn over cardiovascular events, and tesofensine's own trials showed dose-related increases in blood pressure and heart rate. Anyone considering it should weigh that history rather than the weight-loss figure alone.
How it works
Tesofensine inhibits the transporters that clear noradrenaline, dopamine and serotonin from the synapse, raising the levels of all three. Appetite suppression follows from that rather than from any gut hormone pathway.
Because the effect is central and non-selective, it reaches systems that have nothing to do with eating. Raised noradrenaline increases heart rate and blood pressure; raised dopamine affects reward and sleep; raised serotonin affects mood.
This is the same pharmacological family as sibutramine, which was approved for obesity and then withdrawn after a cardiovascular outcomes trial found excess heart attacks and strokes. That history is the most relevant fact about this mechanism.
Regulatory status — United States
Not approved in the United States or the European Union. Development for obesity did not proceed to a completed registration programme in either. Sold as a research chemical, and pharmacologically related to sibutramine, which was withdrawn from major markets over cardiovascular risk.
Last reviewed 18 Aug 2026. Regulatory positions in this category change frequently; we date this line so you can see how current it is.
What it is studied for
Each entry states the evidence behind it. We do not rank indications by effectiveness — for most compounds here, that would be a claim nobody can support.
Weight loss
Clinical trialWhat the obesity trials measured.
EvidenceA phase 2 trial reported roughly 10% weight loss over 24 weeks against placebo, alongside dose-related increases in heart rate and blood pressure.
Parkinson's and Alzheimer's disease
Clinical trialWhat it was originally developed for.
EvidenceFailed to show benefit. Development for both was discontinued.
Identity and clearance
Molecule
- Class
- Small molecule: a triple monoamine reuptake inhibitor, not a peptide
- Molecular weight
- 313.9 Da
Included because it is sold and tracked alongside peptides. It has no chemical relationship to them.
Pharmacokinetics
Clinical trialA very long half-life of around nine days, so levels accumulate for weeks after starting and clear slowly after stopping.
Dose protocols reported in sources
Displayed for reference only. Every row says where it came from, and a trial protocol and a community convention are not the same kind of information. None of this is fed into the calculator, and none of it is a recommendation.
| Goal | Dose | Frequency | Route | Units | Source | Start this protocol |
|---|---|---|---|---|---|---|
| Phase 2 dose range | 250 mcg – 1 mg | Once daily | Oral0.25 mg to 1.0 mg daily in the obesity trials. The largest weight loss came from the highest dose, and so did the largest rise in heart rate and blood pressure. | — | Clinical trial | Start this |
Start this copies a row into a protocol of your own, which you can then edit. Where a source gave a dose range or an ambiguous frequency, those fields arrive empty — we will not pick a number on your behalf.
Safety
Reported effects
- Raised blood pressure and heart rateClinical trial
Dose-related, measured in trials
The defining safety concern, and the mechanism by which the related drug sibutramine caused harm.
- Dry mouthClinical trial
Very common in trials
- InsomniaClinical trial
Common in trials
Expected from raising dopamine and noradrenaline. The nine-day half-life means it does not resolve by skipping an evening dose.
- Mood change, agitation and anxietyClinical trial
Reported in trials
- Cardiovascular outcomes over timeClinical trial
Never established
No cardiovascular outcomes trial was completed. For a drug in this family that is the study that matters, and it is the one that ended sibutramine.
When to stop
- Chest pain, palpitations, breathlessness or a persistently raised heart rate. Seek urgent care.
- Blood pressure higher than your usual readings. Measure it rather than guessing.
- New or worsening anxiety, agitation, or thoughts of harming yourself. Seek help.
- Insomnia that does not settle. Note that the long half-life means stopping takes weeks to clear.
- Any allergic response: rash, hives, facial swelling or difficulty breathing. Seek urgent care.
Interactions and situations that need care
- Any cardiovascular disease, or uncontrolled hypertensionAvoid
This raises heart rate and blood pressure by design. The closely related drug sibutramine was withdrawn from major markets after a cardiovascular outcomes trial found excess heart attacks and strokes, and no equivalent trial has ever been completed for tesofensine.
- MAO inhibitors, SSRIs, SNRIs or other serotonergic drugsAvoid
Combining serotonin reuptake inhibition with another serotonergic drug risks serotonin syndrome, which is a medical emergency. The nine-day half-life means the interaction persists long after stopping.
- Anxiety disorders, bipolar disorder or a history of psychosisAvoid
Raising dopamine and noradrenaline centrally can precipitate or worsen all three, and the long half-life means an adverse reaction cannot be quickly reversed.
- Pregnancy and breastfeedingAvoid
No safety data, and weight loss in pregnancy is contraindicated.
- Stimulants, including high caffeine intakeUse caution
Additive effects on heart rate and blood pressure, which is the axis on which this drug is most likely to cause harm.
What to expect
- Roughly 10% weight loss over 24 weeks in phase 2. A real result, from a mechanism with a bad history.
- It is a stimulant-like small molecule, not a peptide, and shares a mechanism with sibutramine, which was withdrawn over cardiovascular harm.
- The half-life is about nine days. Levels build for weeks after starting, and a side effect does not go away the day you stop.
- No cardiovascular outcomes trial was ever completed. For this family of drug that is the study that decides whether it is safe, and it does not exist.
- If you take it anyway, blood pressure and resting heart rate are the numbers to watch, and watching means measuring.
Storage and handling
- Freeze-dried powder
- Tablets or powder at room temperature, dry and out of light.
- After mixing
- Not applicable. This is taken orally.
Checking your vial
Research chemicals carry no manufacturing standard, so what the vial looks like is often the only quality signal available before you use it. More on assessing quality and COAs.
You cannot assess a tablet or powder by looking at it
No visual check distinguishes this from any other white powder. Third-party testing is the only verification available.
Questions
- Is it a peptide?
- No. It is a small molecule that blocks monoamine reuptake, pharmacologically much closer to a stimulant than to anything else here. It appears here because it is sold and tracked alongside peptides.
- Why was it never approved?
- Development for obesity did not proceed to a completed registration programme in the US or Europe. The trials showed dose-related rises in blood pressure and heart rate, and the closely related drug sibutramine had already been withdrawn over exactly that risk.
- What does a nine-day half-life mean in practice?
- Levels keep rising for several weeks after you start, so the effect you feel in week one is not the effect you will have in week six. And if something goes wrong — stopping takes weeks to clear — not a day.
References
Tesofensine for obesity: phase 2 randomised controlled trial
The Lancet, 2008 · Randomised, double-blind, placebo-controlled phase 2 trial
Adults with obesity · 0.25 mg, 0.5 mg or 1.0 mg orally, once daily · 24 weeks
Dose-dependent weight loss of roughly 5% to 10% against placebo, with dose-related increases in heart rate and blood pressure. Dry mouth, insomnia and mood change were common. No cardiovascular outcomes trial followed.
Related compounds
Semaglutide
A long-acting GLP-1 receptor agonist approved for type 2 diabetes and for weight management, dosed once weekly.
Tirzepatide
A once-weekly dual agonist that activates both the GIP and GLP-1 receptors, approved for type 2 diabetes and for weight management.
Retatrutide
An investigational once-weekly triple agonist acting on the GLP-1, GIP and glucagon receptors. Not approved anywhere.
Liraglutide
The first GLP-1 analogue approved for weight loss. A daily injection, superseded by weekly semaglutide but still the best-documented compound in the class.
Next
What to do with Tesofensine
- Keep a record of itTurn a dose and a schedule into a protocol, then log what you actually take. Tesofensine is filled in for you.
- See what it costsPer-milligram prices read from vendor sites and confirmed by a person, so vial sizes compare.
- Check a combinationWhat our profiles record about Tesofensine alongside each other compound — including the pairs where nothing is recorded.
Keep this page honest
If something here is wrong, out of date, or missing a source, tell us and we will fix it and say that we did.
This page is educational. It describes what published research reports, not what you should do. Peptides discussed here are largely not approved for human use, and nothing on Bioalmanac is medical advice. No clinician reviews these pages.
Page last updated 18 Aug 2026