Tesofensine Dosage Guide

Investigational oral weight-loss compound. Once-daily 0.25 to 1.0 mg protocols from the Phase 2 trials, heart-rate considerations, the Tesomet combination, and safety.

Compiled by PeptideWiki Editorial Team·Last reviewed June 23, 2026

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What Is Tesofensine?

Investigational Drug Warning: Tesofensine (NS2330) is NOT FDA-approved. It is an investigational compound, and the dosing information here comes from published clinical trials, not an approved drug label. It also raises heart rate. Using an unapproved research compound carries inherent risk. Consult a healthcare provider before using it.

Tesofensine (NS2330) is an oral weight-loss compound. It is a triple monoamine reuptake inhibitor, which means it blocks the brain from reabsorbing three appetite-related chemical messengers at once: noradrenaline, dopamine, and serotonin. Leaving more of those active strengthens the brain signals that say you are full, so people feel satisfied sooner and eat less.

This is a different approach from the GLP-1 injections most people know, such as Semaglutide and Tirzepatide, which work through a gut hormone. Tesofensine is a small molecule taken as a once-daily capsule, not a peptide and not an injection. In its main Phase 2 trial, the 0.5 mg dose produced about 9 percent body-weight loss over 24 weeks, roughly double the diet drugs available at the time.

Key Characteristics:

Triple monoamine reuptake inhibitor: keeps noradrenaline, dopamine, and serotonin active for longer to strengthen fullness signals
Oral, once daily: taken as a capsule by mouth, not an injection
Long half-life: about 8 days, so one daily dose maintains a steady level in the body
Brain-appetite mechanism: works on central appetite chemistry rather than the GLP-1 gut-hormone pathway
Raises heart rate: increases resting heart rate by roughly 7 to 8 beats per minute at 0.5 mg
Investigational status: NOT FDA-approved. The obesity program reached Phase 2, not Phase 3

For a complete overview of its mechanism and research, see our full Tesofensine profile. New to this space? Start with the Beginner's Guide to Peptides.

How Tesofensine Dosage Is Determined

Tesofensine dosing comes directly from controlled clinical trials rather than from animal studies and community extrapolation. The pivotal data is the Phase 2 TIPO-1 trial.

TIPO-1 Phase 2 Trial (Astrup et al., Lancet 2008)

The trial enrolled 203 adults with obesity (body-mass index 30 to 40) across five Danish centres. After a 2-week run-in, participants followed an energy-restricted diet and were randomly assigned to tesofensine 0.25, 0.5, or 1.0 mg, or placebo, once daily for 24 weeks. The main outcome was percentage change in body weight.

Group (daily)	Mean Weight Loss	Heart Rate Change
Placebo + diet	−2.0%	No significant change
0.25 mg	−4.5%	No significant change
0.5 mg	−9.2%	+7.4 bpm
1.0 mg	−10.6%	Increased

The 0.5 mg dose produced roughly double the weight loss of the diet drugs approved at the time. The trial authors concluded these results needed confirmation in Phase 3 studies, which were never completed for the obesity program.

Dosing in this guide is derived from published Phase 2 trials. These results were not confirmed in Phase 3.

Tesofensine Dosing Protocols

Tesofensine is taken once daily by mouth. The trials tested fixed doses rather than a gradual increase, but starting at the low dose and assessing tolerance, especially heart rate and sleep, before moving up is the sensible approach.

Dose	Profile	Notes
0.25 mg	Entry dose	Mildest effects. About 4.5 percent weight loss in the trial
0.5 mg	Lead dose	Best balance of efficacy and tolerability. About 9 percent weight loss, with a roughly 7 to 8 bpm heart-rate rise
1.0 mg	Maximum studied	Slightly more weight loss (about 11 percent) but more side effects and a larger heart-rate increase

Start low and check your heart rate. The jump from 0.5 mg to 1.0 mg adds little weight loss but more side effects. Most people get most of the benefit at 0.5 mg. Measure resting heart rate before starting and during use.

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Tesofensine vs GLP-1 Weight-Loss Drugs

Tesofensine works through brain appetite chemistry, a different mechanism from the GLP-1 drugs. The table compares it with Semaglutide and Tirzepatide. Weight-loss figures come from different trials, so they are indicative rather than head-to-head.

Feature	Tesofensine	Semaglutide	Tirzepatide
Mechanism	Brain monoamine reuptake	GLP-1 gut hormone	GLP-1 + GIP
Route	Oral (daily capsule)	Weekly injection	Weekly injection
FDA Status	Investigational (Phase 2)	Approved	Approved
Peak Weight Loss (trial)	~9–11% at 24 weeks	~15–17% at 68 weeks	~22.5% at 72 weeks
Main caution	Raises heart rate	GI side effects	GI side effects
Availability	Research only	Prescription (branded)	Prescription (branded)

Cross-trial comparison caveat: these numbers come from separate trials with different designs and durations. Tesofensine's figures are from a 24-week Phase 2 study, shorter than the GLP-1 trials, and were never confirmed in Phase 3.

For the approved alternatives, see our Semaglutide Dosage Guide and Tirzepatide Dosage Guide.

Forms & Preparation

Unlike injectable peptides, tesofensine is an oral compound, so there is no reconstitution with bacteriostatic water and no syringe. It is supplied as capsules at a fixed strength.

What to know about the form:

Capsule form: research tesofensine is sold as pre-measured capsules, commonly 0.25 mg or 0.5 mg
No reconstitution: nothing to mix or draw up, you take the capsule as supplied
Dose accuracy depends on the source: capsule strength and purity vary between research suppliers, so the actual dose can differ from the label
Storage: keep in a cool, dry place away from light and out of reach of children

Source quality matters. Because tesofensine is not an approved medicine, capsule strength and purity are not regulated. A capsule labeled 0.5 mg may not contain exactly that. This is a meaningful risk for a compound whose effective and high-side-effect doses are close together.

How to Take Tesofensine

Frequency: once daily, every day, by mouth
Time of day: morning is preferred. Tesofensine is stimulating and can cause insomnia if taken later in the day
With or without food: the trials did not require a specific food pairing. Taking it consistently at the same time each day matters more
Half-life: about 8 days, so the level builds up over the first weeks and a single daily dose keeps it steady
Missed dose: because of the long half-life, a single missed day has a small effect. Resume your normal schedule rather than doubling up
Baseline check: measure resting heart rate and blood pressure before starting, and recheck heart rate regularly during use

Build-up matters: with an 8-day half-life, tesofensine keeps accumulating for several weeks after you start. Side effects and heart-rate changes can grow over the first month even at a fixed dose, so do not judge tolerance from the first few days alone.

Tesofensine Dosage by Goal

All trial data is for weight management in adults with obesity.

Balanced Weight Loss (0.5 mg/day)

The lead dose. About 9 percent body-weight loss over 24 weeks with a manageable side-effect profile, though it does raise heart rate by roughly 7 to 8 beats per minute.

Dose: 0.5 mg once daily in the morning
Duration: 24 weeks in the trial
Monitoring: resting heart rate and sleep quality

Conservative Start (0.25 mg/day)

The entry dose. About 4.5 percent weight loss with the mildest effects and no significant heart-rate change. A reasonable starting point before assessing whether to move to 0.5 mg.

Dose: 0.25 mg once daily in the morning
Notes: lowest side-effect burden of the studied doses

Why not 1.0 mg: the 1.0 mg dose added only about 1.4 percentage points of weight loss over 0.5 mg but increased side effects and heart rate. For most people the extra dose is not worth the trade-off.

Tesofensine Treatment Duration

The Phase 2 trials ran for 24 weeks. There is no established long-term protocol because the compound never completed Phase 3.

Phase	Weeks	Description
Build-up	Weeks 1–4	Levels accumulate due to the long half-life. Appetite suppression and any heart-rate change become noticeable
Active Weight Loss	Weeks 4–24	Steady weight reduction. Most loss occurs during this window
Beyond 24 weeks	Not established	No controlled long-term data. The satiety effect also appeared to attenuate over time in the appetite study

Effect may fade: in the appetite-sensation study, the boost in fullness peaked around week 12 and diminished by week 24 even as weight loss continued. Long-term durability is uncertain.

Heart Rate & Cardiovascular Monitoring

The heart-rate effect is tesofensine's defining safety consideration and the main reason it is monitored closely. Because it raises noradrenaline and dopamine activity, it modestly speeds the heart.

Expected effect: resting heart rate rose by about 7 to 8 beats per minute at the 0.5 mg dose in the Phase 2 trial
Blood pressure: did not rise significantly at the 0.25 and 0.5 mg doses, but was monitored throughout
Why Tesomet exists: the combination with metoprolol was created specifically to offset this heart-rate increase, and in that trial there was no significant heart-rate difference from placebo
Who should avoid it: people with significant heart disease, arrhythmias, or uncontrolled high blood pressure

Monitor your heart rate. Check resting heart rate before starting and regularly during use. A sustained, meaningful rise, palpitations, or chest discomfort are reasons to stop and seek medical advice.

Tesomet & Combinations

The studied combination: Tesomet is tesofensine 0.5 mg plus metoprolol 50 mg, designed so the beta-blocker offsets the heart-rate increase. It was tested in a Phase 2 trial in hypothalamic obesity.

Tesomet produced an additional 6.3 percent weight loss versus placebo over 24 weeks in adults with hypothalamic obesity, with no significant heart-rate or blood-pressure difference from placebo. This is the one tesofensine combination with trial evidence behind it.

Combinations to Avoid

Other stimulants: amphetamines, high-dose caffeine, and decongestants add to the heart-rate and blood-pressure effects
MAOI antidepressants: combining a monoamine reuptake inhibitor with an MAOI can cause dangerous serotonin and blood-pressure reactions
Other serotonergic drugs: SSRIs and similar drugs raise the theoretical risk of serotonin excess and should only be combined under medical supervision

Stick to what was studied. Outside the Tesomet combination, there is no trial data for pairing tesofensine with other compounds, and several common combinations are genuinely risky.

Safety, Side Effects & Contraindications

Investigational Compound: Tesofensine is NOT FDA-approved and never completed Phase 3. Long-term safety and cardiovascular outcomes over years are not established. You are assuming risk that has not been fully characterized.

Common Side Effects

Side Effect	Notes
Dry mouth	One of the most common effects. Dose-dependent
Insomnia	Reduced by taking the dose in the morning
Nausea	More common at higher doses
Constipation / hard stools	Increase fluids and fiber
Increased heart rate	About 7 to 8 bpm at 0.5 mg. The key safety signal

Who Should Not Use It

Significant heart disease or arrhythmias: the heart-rate effect is a direct concern
Uncontrolled high blood pressure
Anxiety or panic disorders: the stimulant-like action can worsen these
People taking MAOIs or other stimulants
Pregnancy and breastfeeding: no safety data, avoid entirely

Regulatory status: tesofensine is investigational. The obesity program reached Phase 2, and there is no FDA-regulated product, no standardized dosing label, and no long-term safety surveillance. Any use is inherently investigational.

Common Tesofensine Mistakes

Avoid these errors when using tesofensine:

Starting at the 1.0 mg dose: The 1.0 mg dose produced only slightly more weight loss than 0.5 mg but with more side effects and a larger heart-rate increase. Most of the benefit is captured at 0.5 mg. Start low.

Ignoring heart rate: Tesofensine reliably raises resting heart rate by roughly 7 to 8 beats per minute at 0.5 mg. Without monitoring, a meaningful cardiovascular change can go unnoticed. Check resting heart rate before starting and during use.

Taking it late in the day: Because it is stimulating, taking tesofensine in the afternoon or evening commonly causes insomnia. Morning dosing reduces sleep disruption.

Combining it with other stimulants or MAOIs: Tesofensine already raises noradrenaline, dopamine, and serotonin. Stacking it with other stimulants, decongestants, or MAOI antidepressants risks dangerous over-activation, high heart rate, and blood-pressure spikes.

Expecting approved-drug safety data: Tesofensine never completed a Phase 3 trial. Long-term safety, rare adverse events, and cardiovascular outcomes over years are not established. You are using an investigational compound.

Assuming it works like semaglutide: Tesofensine acts on brain appetite chemistry, not the GLP-1 gut-hormone pathway. Dosing, side effects, and monitoring are different, and the two should not be assumed interchangeable or automatically safe to combine.

Frequently Asked Questions

Tesofensine (also written NS2330) is an investigational oral weight-loss compound. It is a triple monoamine reuptake inhibitor, meaning it keeps three appetite-related brain chemicals (noradrenaline, dopamine, and serotonin) active for longer, which strengthens the feeling of fullness and reduces hunger. It is a small molecule taken as a daily capsule, not a peptide or an injection. It is not FDA-approved.

In the 24-week Phase 2 TIPO-1 trial of 203 adults with obesity, once-daily tesofensine produced mean weight loss of 4.5 percent at 0.25 mg, 9.2 percent at 0.5 mg, and 10.6 percent at 1.0 mg, compared with 2.0 percent on diet plus placebo. The 0.5 mg dose produced roughly double the weight loss of the diet drugs approved at the time. These are Phase 2 results that were never confirmed in a Phase 3 trial.

No. Tesofensine is a small-molecule drug, not a peptide. It is included here because it sits in the same research and weight-management space, similar to how 5-Amino-1MQ and NAD+ are non-peptide research compounds covered alongside peptides. It works on brain chemistry rather than on a peptide receptor.

The Phase 2 trials studied 0.25, 0.5, and 1.0 mg once daily. The 0.5 mg dose is the lead dose because it gave strong weight loss with a more manageable side-effect and heart-rate profile than 1.0 mg. The 1.0 mg dose produced slightly more weight loss but more side effects. Starting low is the standard approach.

No. Tesofensine is investigational and not approved by the FDA or EMA. Its obesity program reached Phase 2 but the original Phase 3 was never completed. It has since been revived as Tesomet (tesofensine combined with a low dose of metoprolol) and studied in Phase 2 for hypothalamic obesity and related conditions. Any tesofensine sold today is a research compound, not a regulated medicine.

Once daily, by mouth. Tesofensine has a long half-life of about 8 days, so it builds up to a steady level in the body and a single daily dose maintains its effect. It is usually taken in the morning because it can disturb sleep if taken later in the day.

The most common side effects in trials were dry mouth, nausea, constipation, hard stools, and trouble sleeping. These were dose-dependent, more frequent at higher doses. The most important cardiovascular effect was an increase in heart rate of about 7 to 8 beats per minute at the 0.5 mg dose. Blood pressure did not rise significantly at the lower doses.

Because it increases noradrenaline and dopamine activity in the body, which are stimulating signals, tesofensine modestly speeds up the heart. This is the main reason a newer formulation, Tesomet, pairs it with metoprolol, a beta-blocker that lowers heart rate, so the two effects offset each other. Anyone using tesofensine should monitor resting heart rate.

Tesomet is a combination of tesofensine 0.5 mg plus metoprolol 50 mg in one daily treatment. The metoprolol is added specifically to counter the heart-rate increase that tesofensine alone causes. In a Phase 2 trial in adults with hypothalamic obesity, Tesomet produced an additional 6.3 percent weight loss versus placebo with no significant heart-rate or blood-pressure difference from placebo.

A dedicated abuse-potential study in recreational stimulant users found that tesofensine's effects were no greater than bupropion or atomoxetine and far below those of amphetamine, indicating a low risk of recreational abuse. That said, it does act on stimulating brain chemicals, so it should not be combined with other stimulants or MAOI antidepressants.

Key Takeaways

Tesofensine is an oral triple monoamine reuptake inhibitor: it raises three appetite-related brain chemicals, a different mechanism from the GLP-1 drugs
Phase 2 results: about 9 percent weight loss at 0.5 mg over 24 weeks, roughly double the diet drugs of its era
0.5 mg is the lead dose: 1.0 mg adds little weight loss but more side effects
It raises heart rate by about 7 to 8 bpm at 0.5 mg, the defining safety consideration
Take it in the morning to limit insomnia, and remember the long 8-day half-life means effects build over weeks
Tesomet pairs it with metoprolol to offset the heart-rate effect, the only studied combination
NOT FDA-approved: the obesity program reached Phase 2, not Phase 3

This article is for educational and informational purposes only. See our Disclaimer.

References

Astrup A, et al. “Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial.” Lancet. 2008;372(9653):1906-1913. PubMed
Gilbert JA, et al. “The effect of tesofensine on appetite sensations.” Obesity (Silver Spring). 2011;20(3):553-561. PubMed
Huynh K, et al. “Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity.” Eur J Endocrinol. 2022;186(6):687-700. PubMed
Schoedel KA, et al. “Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users.” Clin Pharmacol Ther. 2010;88(1):69-78. PubMed
Hauser RA, et al. “Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson disease.” Mov Disord. 2007;22(3):359-365. PubMed

Next Steps

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