Dashnaiv Peptides
Compounds·metabolic other·triple monoamine reuptake inhibitor

Tesofensine: what the obesity and Parkinson's trials found, why it is not a peptide, and where the Mexican approval stands

What 63 indexed publications and 12 randomized trials actually state about tesofensine, sentence by sentence, each tied to its source and labeled by the kind of evidence it is.

Human clinical trial Reviewed 23 sources Updated

At a glance

Evidence availability
Human clinical evidence
Strongest tier in the indexed literature
Indexed publications
63
Europe PMC, title or abstract, 2026-09-14
Human studies in ledger
12
9 randomized; study count, not efficacy proof
Approval
not approved
ChEMBL phase 2
Routes reported
intravenous, oral, subcutaneous
from studies in this ledger
Studied in
Humans, Mice, Rats
19 primary studies in the evidence table
Reviewed by Adam Mirando, PharmD, on . What changed

What tesofensine is, and why it is not a peptide

Tesofensine is a small molecule in the metabolic other class (triple monoamine reuptake inhibitor). Europe PMC indexes 63 publications naming it or a listed alias in a title or abstract, including 12 randomized controlled trials and 7 clinical trials of any design, as of . The strongest evidence tier in that literature is human clinical trials.

This page reports what those studies state, sentence by sentence, with each statement tied to its source and labeled by the kind of evidence it is. It does not recommend use, and it does not translate study doses into anything personal.

What the evidence level means

Publication counts show what is indexed, not how strong the evidence is. The ledger below separates human clinical records from preclinical, analytical, and in-vitro work.

Human clinical studies in this ledger129 randomized · 3 other human clinical
Evidence strengthNot yet assessedSeparate from evidence availability
Efficacy signalNot yet assessedRead the study result, not the tier alone

Interpretation boundary: An indexed publication count is a discovery measure. It does not establish efficacy, safety, approval, or a personal treatment plan.

Tesofensine in two minutes

What it is. A small-molecule tablet drug from Denmark that blocks the reuptake of serotonin, noradrenaline and dopamine. Not a peptide, whatever the capsule label says. Developed for Alzheimer's and Parkinson's disease, where it failed; repurposed for obesity when trial patients lost weight.

What the research actually shows. 63 indexed publications. One 24-week phase 2 trial in 203 obese adults: 9.2% weight loss at 0.5 mg and 10.6% at 1.0 mg against 2.0% on placebo, the largest oral result of its era. Three Parkinson's trials with no useful benefit. One 24-week trial of the metoprolol combination in 21 people with hypothalamic obesity. A 372-patient phase 3 in Mexico reported by the developer at about 10% and not yet published.

The catch. Heart rate up to about 8 beats a minute, blood pressure up at 1.0 mg, insomnia in half of those treated, dry mouth in four in ten. Its class-mate sibutramine was withdrawn for cardiovascular harm; no outcomes trial of tesofensine exists.

Status. Approved nowhere. A Mexican application received a favourable opinion in 2023, was withheld in November 2024 and was resubmitted in 2025. Prohibited in competition by WADA as a stimulant.

Where the evidence is thinnest. Anything beyond 24 weeks, cardiovascular outcomes, and the capsules people buy, whose content nobody has tested.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

How tesofensine works: three transporters, one appetite circuit

Written from general pharmacology and the development record, and marked as editorial synthesis; the measurements behind it are quoted in the biomarker section.

  • Tesofensine is a small synthetic molecule from the phenyltropane family, not a peptide: it has no amino acids, is taken as a tablet, is absorbed through the gut and lasts about ten days in the body, none of which is true of the injectable peptides it is sold beside. The 'tesofensine peptide' label on vendor pages is a category error that tells the buyer nothing about what is in the capsule.Editorial synthesis
    Editorial synthesis from general knowledge
  • It blocks the transporters that recycle serotonin, noradrenaline and dopamine back into neurons, so all three stay longer in the synapse; that is the triple reuptake inhibition in its class name, shared in part with sibutramine (noradrenaline and serotonin) and bupropion (noradrenaline and dopamine). Its active metabolite M1 does the same and lasts longer. In rats, the appetite effect runs through dopamine D1 and noradrenaline alpha-1 receptors and, in a 2024 study, through silencing of GABA-releasing neurons in the lateral hypothalamus, the circuit that drives feeding.Editorial synthesis
    Editorial synthesis from general knowledge
  • The consequence of the same pharmacology is the safety profile: more noradrenaline means a faster heart and, at higher doses, higher blood pressure, plus dry mouth and insomnia; more dopamine and serotonin in the wrong people means agitation and mood effects, which is why psychiatric history was an exclusion. Its ten-day half-life means every effect, wanted or not, builds over four to six weeks and takes as long to leave.Editorial synthesis
    Editorial synthesis from general knowledge

What happened in the human studies?

This record's ledger holds 12 primary human studies, of which 10 are trials. Few enough to show in full: each card quotes what its abstract reported about Tesofensine. Read them before any other section on this page.

  • Randomized controlled trial humans 2022 Human clinical trial
    No significant differences in heart rate or blood pressure were observed between groups.
    Source pmid-35294397 · quoted verbatim from the abstract
  • Clinical trial humans 2011 Human clinical trial
    Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months.
    Source pmid-21197148 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2010 Human clinical trial
    The aim of this analysis was to exemplify the QP-A by eventually predicting the clinical outcome of a proof-of-concept (PoC) trial of tesofensine in AD patients from two small phase IIa trials.
    Source pmid-20077053 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2009 Human clinical trial
    Treatment with Tesofensine resulted in a mean weight reduction of 4.5, 9.2 and 10.6% higher than that of placebo for 0.25, 0.5 and 1.0 mg, respectively.
    Source pmid-19824222 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2009 Human clinical trial
    Coadministration of cholestyramine resulted in a predicted 56% withdrawal of meloxicam from the EHC process causing a reduction in the t((1/2)) from approximately 19 hours to approximately 12 hours.
    Source pmid-19705923 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2008 Human clinical trial
    Tesofensine 0.25 mg, 0.5 mg, and 1.0 mg and diet induced a mean weight loss of 4.5% (0.87), 9.2% (0.91), and 10.6% (0.84), respectively, greater than diet and placebo (p Interpretation Our results suggest that tesofensine 0.5 mg might have the potential to produce a weight loss twice that of currently approved drugs.
    Source pmid-18950853 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2008 Human clinical trial
    Gastrointestinal tract and neuropsychiatric adverse events were more frequent with tesofensine than with placebo, especially at the higher dosages.
    Source pmid-18474731 · quoted verbatim from the abstract
  • Randomized controlled trial humans n = 320 2007 Human clinical trial
    However, simulations performed revealed that only CL(CR) and sex had a significant effect on the steady-state plasma concentration-time profiles.
    Source pmid-17324246 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2007 Human clinical trial
    At the dosages tested, NS 2330 did not provide significantly greater benefit than placebo.
    Source pmid-17149725 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2004 Human clinical trial
    Moreover, NS 2330 coadministration did not appear to alter dyskinesia severity or the duration of the antiparkinsonian response to levodopa.
    Source pmid-15390018 · quoted verbatim from the abstract
  • Human study humans 2013 Observational, human
    Sibutramine was associated with an increase in major adverse cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial and it was withdrawn from the market in 2010.
    Source pmid-25114779 · quoted verbatim from the abstract
  • Human study humans n = 28 2010 Observational, human
    Inhibition resulted in reduced clearances and prolonged elimination half-lives for tesofensine and itraconazole: using NCA, the actual study revealed an approximately 9% increase in exposure for the timeframe of the coadministration with itraconazole (the area under the plasma concentration-time curve (AUC) from 0 to 144 hours [AUC(144h)]), and the impact on exposure estimated to infinity (AUC(infinity)) was approximately 26%.
    Source pmid-20000889 · quoted verbatim from the abstract

Trial by trial: what tesofensine did, and where it failed

Every human study in the ledger. The Parkinson's rows are where the drug came from; the obesity row is why anyone still talks about it.

Human studies of tesofensine in the ledger.
TrialParticipantsDose and durationPrimary endpointResult
Astrup 2008 (Lancet phase 2)203 obese adults, five Danish centres0.25, 0.5 or 1.0 mg oral daily with diet, 24 weeksBody weight4.5%, 9.2%, 10.6% loss vs 2.0% placebo; 79% completed; heart rate and blood pressure rose (full text)
Nielsen 2009Same trial, Danish secondary publicationAs aboveBody weight and compositionSame figures; authors call for phase 3 confirmation of safety
Huynh 2022 (Tesomet)21 adults with hypothalamic obesity0.5 mg + metoprolol 50 mg daily, 24 weeksSafetyWeight reduced vs placebo; no heart-rate or blood-pressure change; sleep disturbance 50%, dry mouth 43%, headache 36%; one anxiety SAE
Hauser 2007261 early Parkinson's patients0.25, 0.5 or 1.0 mg daily, 14 weeksUPDRS scoreNo significant benefit at any dose
Rascol 2008 (ADVANS)Advanced Parkinson's with motor fluctuations0.125 to 1 mg daily, 14 weeksUPDRS and off timeModest gains at 0.5 and 0.25 mg without dose-response; GI and psychiatric events more frequent at higher doses
Bara-Jimenez 20049 advanced Parkinson's patientsSingle dose, with and without levodopaParkinsonian scoresNo change; well tolerated
Lehr 2010 (Alzheimer's modelling)62 mild Alzheimer's patients in two 4-week trialsNot stated in the abstractCognition (modelled)Model predicted the proof-of-concept outcome; development in Alzheimer's ended
Lehr 2007 (population PK)320 Alzheimer's patientsMultiple oral dosesPharmacokineticsHalf-lives 234 h and 374 h (drug and metabolite); weight, sex, kidney function, BMI and age influence exposure
Lehr 2009 (enterohepatic model)21 healthy volunteersSingle 6-hour infusion, 0.3 to 1.2 mgPharmacokineticsMultiple plasma peaks explained by bile recirculation
Lehr 2010 (itraconazole)28 healthy volunteersSingle 2 mg oral dose, half with itraconazoleDrug interactionAbout 9% higher exposure with the CYP3A4 inhibitor
Krug 2026Anti-doping urine study483 mcg single dose (from the record)Metabolite identificationMetabolites characterised for doping control; S6 stimulant, in-competition
Medix phase 3 (developer's report; not in ledger)372 adults with obesity, Mexico0.25 and 0.5 mg daily, 24 weeksBody weightAbout 10% loss; more than half lost over 10%; unpublished

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

What the evidence shows

One row per primary study in this record's ledger. Fields are read from each paper's indexing and abstract. "Analytical method" marks papers about detecting or measuring the compound rather than about its effects.

19 primary studies in this record's ledger, strongest evidence first. A dash means the abstract did not state the value.
StudyDesignnSpeciesDoseRouteDurationReported outcomeTier
Huynh 2022 Randomized controlled trial — Humans0.5 mg—— No significant differences in heart rate or blood pressure were observed between groups. Human clinical trial
Ioannides-Demos 2011 Clinical trial — Humans——12 months Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5… Human clinical trial
Lehr 2010 Randomized controlled trial — Humans——— — Human clinical trial
Nielsen 2009 Randomized controlled trial — Humans0.5 mg—24 weeks Treatment with Tesofensine resulted in a mean weight reduction of 4.5, 9.2 and 10.6% higher than that of placebo for 0.25, 0.5 and 1.0 mg, respectively. Human clinical trial
Lehr 2009 Randomized controlled trial — Humans1.2 mgintravenous— Coadministration of cholestyramine resulted in a predicted 56% withdrawal of meloxicam from the EHC process causing a reduction in the t((1/2)) from approximately 19 hours to approximately 12 hours. Human clinical trial
Astrup 2008 Randomized controlled trial — Humans0.25 mg; 0.5 mg—6 months Tesofensine 0.25 mg, 0.5 mg, and 1.0 mg and diet induced a mean weight loss of 4.5% (0.87), 9.2% (0.91), and 10.6% (0.84), respectively, greater than diet and placebo (p Interpretation Our results suggest that… Human clinical trial
Rascol 2008 Randomized controlled trial — Humans0.5 mg; 0.25 mg—14 weeks Gastrointestinal tract and neuropsychiatric adverse events were more frequent with tesofensine than with placebo, especially at the higher dosages. Human clinical trial
Lehr 2007 Randomized controlled trial 320 Humans—oral— However, simulations performed revealed that only CL(CR) and sex had a significant effect on the steady-state plasma concentration-time profiles. Human clinical trial
Hauser 2007 Randomized controlled trial — Humans0.25 mg; 0.5 mg—5 years At the dosages tested, NS 2330 did not provide significantly greater benefit than placebo. Human clinical trial
Bara-Jimenez 2004 Randomized controlled trial — Humans——— Moreover, NS 2330 coadministration did not appear to alter dyskinesia severity or the duration of the antiparkinsonian response to levodopa. Human clinical trial
Krug 2026 Analytical method — Humans483 μg—— Tesofensine (NS-2330) is a pharmacologically active compound with weight-reducing effects in obese patients. Observational, human
Cheung 2013 Human study — Humans——— Sibutramine was associated with an increase in major adverse cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial and it was withdrawn from the market in 2010. Observational, human
Lehr 2010 Human study 28 Humans2 mgoral6 days; 5 days Inhibition resulted in reduced clearances and prolonged elimination half-lives for tesofensine and itraconazole: using NCA, the actual study revealed an approximately 9% increase in exposure for the timeframe of the… Observational, human
Lopez 2025 Animal study — Rats——— However, in contrast, female rats demonstrated greater and more homogenous weight loss than males following the administration of diethylpropion and tesofensine. Animal, preclinical
Perez 2024 Animal study — Rats, Mice——— We found that tesofensine induces a greater weight loss in obese rats than lean rats, while differentially modulating the neuronal ensembles and population activity in LH. Animal, preclinical
Axel 2010 Animal study — Rats2.0 mg/kg; 0.5-3.0 mg/kgsubcutaneous16 days DIO rats treated with tesofensine (2.0 mg/kg, s.c.) for 16 days showed significantly lower body weights than vehicle-treated DIO rats, being reflected by a marked hypophagic response. Animal, preclinical
Lehr 2008 Animal study 228 Mice——— EC(50) values of M1, as an inhibitor of the dopamine transporter, were 4-5-fold higher than those for tesofensine in mice. Animal, preclinical
Larsen 2007 Animal study — Rats——5 days; 14 days We find that chronic, but not sub-chronic treatment with Tesofensine increases BDNF mRNA in the CA3 region of the hippocampus (35%), and Arc mRNA in the CA1 of the hippocampus (65%). Animal, preclinical
Li 2025 In vitro study — Humans——— — Mechanistic, in vitro

Doses reported in studies

Each entry is a sentence quoted from the study's abstract, with the study's design, sample size and year in front of it. Comparator doses in the same sentence are not attributed to tesofensine.

  • Obese adults took 0.25, 0.5 or 1.0 mg once daily with diet for 24 weeks, losing 4.5%, 9.2% and 10.6% of body weight against 2.0% on diet and placebo.Human clinical trial
    Source pmid-18950853
  • The combination Tesomet paired 0.5 mg tesofensine with 50 mg metoprolol once daily for 24 weeks in hypothalamic obesity.Human clinical trial
    Source pmid-35294397
  • Early Parkinson's patients took 0.25, 0.5 or 1.0 mg daily for 14 weeks.Human clinical trial
    Source pmid-17149725
  • Advanced Parkinson's patients took 0.125, 0.25, 0.5 or 1 mg once daily for 14 weeks.Human clinical trial
    Source pmid-18474731
  • Healthy volunteers received single six-hour infusions of 0.3 to 1.2 mg in a rising-dose pharmacokinetic study.Human clinical trial
    Source pmid-19705923
  • Twenty-eight volunteers took a single 2 mg oral dose, half of them with itraconazole.Observational, human
    Source pmid-20000889

Every tesofensine dose in the trials, in one table

Every figure here was given in a trial. The vendor capsules print the same numbers; that does not make them the trial drug.

Doses of tesofensine administered in studies.
SettingRouteDoseScheduleNote
Obesity phase 2Oral tablet0.25, 0.5, 1.0 mgOnce daily, 24 weeks1.0 mg raised blood pressure and dropouts; dropped from phase 3
Obesity phase 3 (Mexico, unpublished)Oral tablet0.25, 0.5 mgOnce daily, 24 weeksDeveloper's report
Hypothalamic obesity (Tesomet)Oral tablet0.5 mg with metoprolol 50 mgOnce daily, 24 weeksBeta-blocker added to blunt heart rate
Parkinson's diseaseOral tablet0.125 to 1.0 mgOnce daily, 14 weeksNo useful benefit; more adverse events at higher doses
PharmacokineticsIntravenous infusion0.3 to 1.2 mg over 6 hoursSingleHealthy volunteers
Drug interactionOral2 mgSingleHealthy volunteers, with itraconazole
Rats (diet-induced obesity)Subcutaneous2.0 mg/kg; 0.5 to 3.0 mg/kg16 daysAppetite suppression via dopamine D1 and alpha-1 receptors

Nothing on this page is an instruction to take anything. The trial doses are a matter of record; the products sold at those doses are unregulated, and the drug they contain has no approval because of what it does to heart rate and blood pressure at exactly these amounts.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Side effects: what the trials recorded, with frequencies

From placebo-controlled trials, with frequencies where the abstracts give them. Dry mouth, insomnia, headache and nausea lead; heart rate and, at 1.0 mg, blood pressure are the reason the drug has no approval. Events and their frequency as each study reported them, with the denominator where the abstract gives one.

  • In the Tesomet trial, sleep disturbance affected 50% on treatment against 13% on placebo, dry mouth 43% against 0%, and headache 36% against 0%; one participant stopped after worsened pre-existing anxiety.Human clinical trial
    Source pmid-35294397
  • With metoprolol in the combination, heart rate and blood pressure did not change.Human clinical trial
    Source pmid-35294397
  • In advanced Parkinson's disease, gastrointestinal and neuropsychiatric adverse events were more frequent at higher doses, without a dose-response for benefit.Human clinical trial
    Source pmid-18474731
  • The 2008 obesity trial's authors called for phase 3 confirmation of both efficacy and safety.Human clinical trial
    Source pmid-18950853
  • The finding that decided the drug's fate is in the Lancet full text rather than its abstract: at the two lower doses heart rate rose by up to about 8 beats per minute and blood pressure by 1 to 3 mmHg, and the 1.0 mg dose raised blood pressure further with more dropouts, which is why the Mexican phase 3 tested only 0.25 and 0.5 mg and why the metoprolol combination exists. The class history matters: sibutramine, another noradrenaline-serotonin reuptake inhibitor for obesity, was withdrawn in 2010 after a cardiovascular outcomes trial; no outcomes trial of tesofensine exists.Editorial synthesis
    Editorial synthesis from general knowledge · primary document to be added to the ledger
  • A 2026 anti-doping study notes tesofensine is still under regulatory review yet marketed online as a dietary supplement, and is prohibited in competition as an S6 stimulant.Observational, human
    Source pmid-42320973

Who tesofensine is discussed for, and the cautions that recur

Studied: obese adults without major illness, people with hypothalamic obesity, and people with Parkinson's or Alzheimer's disease. Excluded or unstudied: anyone with cardiovascular disease, uncontrolled blood pressure, psychiatric illness, or on other monoamine drugs; anyone under 18; pregnancy; anyone beyond 24 weeks. Community: people wanting an oral alternative to GLP-1 injections.

The cautions follow from the pharmacology and the trials:

  • Heart rate and blood pressure. Both rose in the phase 2; the 1.0 mg dose was abandoned for it; the combination with a beta-blocker exists because of it. Sibutramine, the nearest approved relative, was withdrawn after a cardiovascular outcomes trial. No such trial exists for tesofensine.
  • Sleep and mood. Insomnia in half of those treated in the Tesomet trial; one serious worsening of anxiety; more neuropsychiatric events at higher doses in Parkinson's patients.
  • Other serotonergic or dopaminergic drugs. Antidepressants, stimulants, MAO inhibitors and triptans act on the same transmitters; no interaction study exists beyond itraconazole and levodopa.
  • The ten-day half-life. A dose taken today is still acting in a month. Side effects that appear in week four cannot be stopped quickly.
  • Tested athletes. Prohibited in competition as an S6 stimulant; with a ten-day half-life, an out-of-competition dose can produce an in-competition positive.
  • The product. Capsules sold as 'tesofensine peptide' or 'supplement' are neither; nobody has verified what they contain.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Biomarkers measured in studies

Laboratory and clinical measures the studies report tracking, including which hormones did and did not change.

  • Clinical trial humans 2011 Human clinical trial
    This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide).
    Source pmid-21197148 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2009 Human clinical trial
    The aim of this analysis was to accomplish a model that is able to describe typical plasma concentration-time profiles of compounds undergoing EHC using data from intravenous studies of tesofensine and meloxicam.
    Source pmid-19705923 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2008 Human clinical trial
    Gastrointestinal tract and neuropsychiatric adverse events were more frequent with tesofensine than with placebo, especially at the higher dosages.
    Source pmid-18474731 · quoted verbatim from the abstract
  • Randomized controlled trial humans n = 320 2007 Human clinical trial
    Plasma concentration-time profiles of NS2330 and M1 were best described by one-compartment models with first-order elimination for both compounds.
    Source pmid-17324246 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2004 Human clinical trial
    Moreover, NS 2330 coadministration did not appear to alter dyskinesia severity or the duration of the antiparkinsonian response to levodopa.
    Source pmid-15390018 · quoted verbatim from the abstract
  • Human study humans 2026 Observational, human
    Due to its impact on body weight, tesofensine could be relevant in competitive sports, particularly in weight-class disciplines and sports where power-to-weight ratio is decisive.
    Source pmid-42320973 · quoted verbatim from the abstract

Reported interactions

Sentences in which the compound is studied alongside another agent. Read the quotation: the word interaction can also be statistical.

  • Randomized controlled trial humans 2004 Human clinical trial
    Moreover, NS 2330 coadministration did not appear to alter dyskinesia severity or the duration of the antiparkinsonian response to levodopa.
    Source pmid-15390018 · quoted verbatim from the abstract
  • Human study humans n = 28 2010 Observational, human
    Overall, 28 subjects received a single oral dose of tesofensine 2 mg; 14 of these subjects were coadministered an oral itraconazole 400 mg loading dose and a 200 mg maintenance dose for 6 days before and 5 days after administration of tesofensine.
    Source pmid-20000889 · quoted verbatim from the abstract
  • Itraconazole, a CYP3A4 inhibitor, raised tesofensine exposure by about 9% during co-administration, a modest interaction for a drug with such a long half-life.Observational, human
    Source pmid-20000889

Reported timelines

Onset, peak and duration figures as each study reported them.

  • Population modelling gave half-lives of 234 hours for tesofensine and 374 hours for its active metabolite M1, about ten and sixteen days.Human clinical trial
    Source pmid-17324246
  • Plasma levels show multiple peaks because the drug recirculates through the bile.Human clinical trial
    Source pmid-19705923
  • Weight loss in the obesity trial was measured at 24 weeks; the Parkinson's trials measured at 14 weeks.Human clinical trial
    Source pmid-18950853

What is measured over time, and what is not

The pharmacokinetics set the clock. With half-lives of 234 hours for the drug and 374 hours for its metabolite, blood levels climb for four to six weeks before they plateau, so appetite suppression, insomnia and heart-rate effects all build rather than arriving on day one, and all persist for weeks after the last tablet. Weight was measured at 24 weeks in both obesity trials and at 14 weeks in Parkinson's disease. Nothing was measured beyond 24 weeks: not weight regain after stopping, not blood pressure over a year, not cardiovascular events. 'How long does it take to feel it' has an answer of days for appetite and weeks for full effect; 'what happens after six months' has none.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Study durations

Treatment and follow-up periods as stated in each abstract.

  • Randomized controlled trial humans 2009 Human clinical trial
    Durations stated: 24 weeks
    In total 203 obese persons were randomised to treatment with Tesofensine 0.25, 0.5, or 1.0 mg, or placebo daily for 24 weeks.
    Source pmid-19824222 · quoted verbatim from the abstract, emphasis added
  • Randomized controlled trial humans 2008 Human clinical trial
    Durations stated: 6 months
    Weight-loss drugs produce an additional mean weight loss of only 3-5 kg above that of diet and placebo over 6 months, and more effective pharmacotherapy of obesity is needed.
    Source pmid-18950853 · quoted verbatim from the abstract, emphasis added
  • Randomized controlled trial humans 2008 Human clinical trial
    Durations stated: 14 weeks
    Tesofensine (0.125, 0.25, 0.5, or 1 mg) or placebo tablets were administered once daily for 14 weeks.
    Source pmid-18474731 · quoted verbatim from the abstract, emphasis added
  • Randomized controlled trial humans 2007 Human clinical trial
    Durations stated: 5 years
    Two hundred sixty-one subjects with PD < 5 years and not receiving dopaminergic treatment were randomly assigned to daily treatment with NS 2330 at 0.25 mg, 0.5 mg, 1.0 mg, or placebo.
    Source pmid-17149725 · quoted verbatim from the abstract, emphasis added
  • Human study humans n = 28 2010 Observational, human
    Durations stated: 6 days; 5 days
    Overall, 28 subjects received a single oral dose of tesofensine 2 mg; 14 of these subjects were coadministered an oral itraconazole 400 mg loading dose and a 200 mg maintenance dose for 6 days before and 5 days after administration of tesofensine.
    Source pmid-20000889 · quoted verbatim from the abstract, emphasis added

Routes: oral tablets in every efficacy trial

Oral, once daily, in every efficacy trial; intravenous infusion only in pharmacokinetic studies. It is a tablet drug, and 'injectable tesofensine' has no study behind it. Routes of administration named in each study.

  • Randomized controlled trial humans 2009 Human clinical trial
    administration by intravenous route reported
    The aim of this analysis was to accomplish a model that is able to describe typical plasma concentration-time profiles of compounds undergoing EHC using data from intravenous studies of tesofensine and meloxicam.
    Source pmid-19705923 · quoted verbatim from the abstract
  • Randomized controlled trial humans n = 320 2007 Human clinical trial
    administration by oral route reported
    Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM.
    Source pmid-17324246 · quoted verbatim from the abstract
  • Human study humans n = 28 2010 Observational, human
    administration by oral route reported
    Overall, 28 subjects received a single oral dose of tesofensine 2 mg; 14 of these subjects were coadministered an oral itraconazole 400 mg loading dose and a 200 mg maintenance dose for 6 days before and 5 days after administration of tesofensine.
    Source pmid-20000889 · quoted verbatim from the abstract
  • Animal study rats 2010 Animal, preclinical
    administration by subcutaneous route reported
    DIO rats treated with tesofensine (2.0 mg/kg, s.c.) for 16 days showed significantly lower body weights than vehicle-treated DIO rats, being reflected by a marked hypophagic response.
    Source pmid-20200509 · quoted verbatim from the abstract

Weight-normalized doses, as published

Per-kilogram figures exactly as each study published them, for the species it studied.

  • Animal study rats 2010 Animal, preclinical
    Weight-normalized doses as published: 2.0 mg/kg; 0.5-3.0 mg/kg; 1.5 mg/kg; 0.3 mg/kg
    DIO rats treated with tesofensine (2.0 mg/kg, s.c.) for 16 days showed significantly lower body weights than vehicle-treated DIO rats, being reflected by a marked hypophagic response.
    Source pmid-20200509 · quoted verbatim from the abstract, emphasis added

Weight-normalized figures above are reproduced exactly as each study published them, for the species it studied. Dose does not scale linearly with body mass between species: metabolic rate, clearance and receptor density differ, and regulatory guidance uses allometric, not proportional, conversion. A mg/kg figure from a rat study is a fact about that rat study and nothing else.

What people report outside the literature

Forum reports describe appetite suppression, insomnia and dry mouth on capsules sold as 'tesofensine peptide'. The compound is not a peptide, the products are unregulated, and no study has tested them. What circulates in user communities and clinic marketing, reported so a reader knows the figures and their origin. None of it has been tested in a trial, and none of it is a suggestion.

  • Tesofensine circulates as an oral weight-loss aid, sold as capsules or tablets at 0.25 to 0.5 mg on Amazon and vendor sites under 'peptide' and 'supplement' labels, and discussed on a dedicated subreddit. Reports describe strong appetite suppression within days, insomnia, dry mouth, a racing heart in some, and irritability; several describe a plateau after two or three months and a slow return of appetite after stopping, which fits a ten-day half-life. None of this comes from a study of those products, whose content is unverified; the trial doses are in the table above and are the same numbers the vendors print.Editorial synthesis
    Editorial synthesis from general knowledge
Method note · shared across compounds

Reconstitution mathematics

Lyophilised peptide is supplied as a mass in a vial and dissolved in a stated volume of diluent. Two figures follow from that and nothing else:

  • Concentration = mass in vial ÷ diluent volume. A 5 mg vial in 2 mL is 2.5 mg/mL, or 2,500 mcg/mL.
  • Volume for a given mass = that mass ÷ concentration. 250 mcg at 2,500 mcg/mL is 0.1 mL. On a U-100 insulin syringe, where 1 mL is 100 units, that is 10 units.

Study doses on this page are quoted as published, in the units the authors used. Converting between mcg, mg and IU, or between a mass and a syringe volume, is arithmetic; deciding a mass is not, and this page does not do it. The reconstitution calculator performs the conversion with the formula shown.

Method note · shared across compounds

Reading a certificate of analysis

A certificate of analysis is a laboratory report on one batch. Reading it means checking four things in order.

  1. Identity. Mass spectrometry should report an observed molecular mass matching the peptide's theoretical mass within the instrument's stated tolerance. A certificate with no mass spectrometry, or one that lists only the expected value, has not confirmed identity.
  2. Purity. HPLC purity is the area of the main peak as a share of all peaks, at a stated wavelength. It says nothing about what the other peaks are, and it is not a measure of quantity.
  3. Quantity. Net peptide content, by amino acid analysis or UV, is the fraction of the vial's mass that is peptide rather than counter-ions and water. A 5 mg vial at 80% net content holds 4 mg of peptide, and every concentration figure above changes accordingly.
  4. Provenance. The batch number on the certificate should match the vial, the laboratory should be named and independent of the seller, and the test date should be recent.

This page rates no supplier and links to none. It describes how to read the document.

Method note · shared across compounds

Equipment described in studies

Published human studies of injectable peptides report the same small set of materials: single-use insulin syringes with fixed needles, most often U-100 with 29 to 31 gauge needles; bacteriostatic water or sterile water for injection as diluent, with the choice stated in the methods; alcohol swabs; and refrigerated storage of reconstituted solution. Animal studies more often report intraperitoneal or intragastric administration and state the vehicle used. Where a study in this record's ledger names its materials or vehicle, that sentence appears under storage or routes above; where it does not, nothing is assumed here.

Storage and handling

Tesofensine is a stable small molecule supplied as tablets in every trial; it needs no reconstitution and no refrigeration, and pages offering a 'reconstitution guide' for it have confused it with the peptides they sell alongside. Products sold online carry no verified storage or content data.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Common mistakes in how tesofensine is discussed

  1. Calling it a peptide. It is a phenyltropane small molecule taken as a tablet. The label is a sales category, not chemistry.
  2. Saying it is approved in Mexico. The developer's filings show a favourable opinion in 2023, approval withheld in November 2024 and a resubmission in 2025. No approval is documented as of this page's date.
  3. Quoting the 1.0 mg result without its cost. The highest dose produced 10.6% loss and raised blood pressure enough to be dropped from phase 3.
  4. Reading 24 weeks as long-term. No trial has followed anyone longer, and the drug's class was withdrawn once on cardiovascular outcomes data that took years to gather.
  5. Comparing it with semaglutide on weight alone. The GLP-1 drugs have cardiovascular outcome trials showing benefit; tesofensine has a heart-rate signal and no outcomes trial.
  6. Treating the ten-day half-life as convenience. It means slow onset, slow offset, and a positive doping test long after the last dose.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Tesofensine vs semaglutide, tirzepatide, phentermine and sibutramine

Tesofensine beside the weight-loss drugs it is compared with, from their own records where one exists.
DrugClass and routeWeight loss in trialsCardiovascular recordStatus
TesofensineTriple monoamine reuptake inhibitor; oral9.2% at 0.5 mg, 10.6% at 1.0 mg vs 2.0% placebo, 24 weeks (phase 2)Heart rate and blood pressure up; no outcomes trialNot approved; Mexican application pending
SemaglutideGLP-1 receptor agonist; weekly injection; 6039 indexed publications, 305 randomized trialsAbout 15% at 68 weeks in its pivotal trialOutcomes trial showed fewer cardiovascular eventsApproved 2017
TirzepatideGIP/GLP-1 agonist; weekly injection; 2756 indexed publications, 131 randomized trialsAbout 15 to 21% at 72 weeksOutcomes trial completedApproved 2022
PhentermineNoradrenaline-releasing stimulant; oralAbout 5% over placebo in short trialsHeart rate up; approved for short-term use onlyApproved (US) for up to 12 weeks; no record on this site
SibutramineNoradrenaline-serotonin reuptake inhibitor; oralAbout 4 to 5% over placeboWithdrawn 2010 after more cardiovascular events in the SCOUT trialWithdrawn; no record on this site
AOD-9604 and SLU-PP-332This site's other 'metabolic, other' compounds; 25 and 12 indexed publicationsAOD-9604: no effect in its phase 2; SLU-PP-332: mice onlyNoneNot approved

The honest comparison is with sibutramine, not semaglutide: same class, same heart-rate signal, and a withdrawal that came only after a long outcomes trial. The GLP-1 drugs sit in a different evidential world. No trial has compared tesofensine with any of them.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Other compounds in its class

Same class in the registry: AOD-9604, SLU-PP-332. Each row shows what that compound's own record states; nothing is inferred across rows.

3 compounds in the metabolic other class. Each row states what that compound's own record says; nothing is inferred across rows.
CompoundTierPublicationsRCTsRecord
Tesofensine Human clinical trial 63 12 draft
AOD-9604 Human clinical trial 25 0 draft
SLU-PP-332 Observational, human 12 0 draft

Regulatory status: not approved anywhere; the Mexican application

Registry facts only. Jurisdiction-level status, compounding categories and sport prohibitions need their own cited documents before they appear here.

  • Not approved anywhere as of the sources available on 2026-09-24. NeuroSearch stopped development after the 2008 phase 2; Saniona later licensed it to Medix, which ran a phase 3 in Mexico (372 patients, 0.25 and 0.5 mg, about 10% weight loss at 24 weeks, by the developer's report) and applied to COFEPRIS. The agency's technical committee gave a favourable non-binding opinion in February 2023, withheld approval in November 2024, and Medix resubmitted the dossier in 2025. A ranking page states it was approved in Mexico in 2023; the developer's own filings say otherwise. Not approved by FDA or EMA and not in development there. The WADA Prohibited List classes it under S6 stimulants, prohibited in competition. Sold online as a supplement, which a 2026 anti-doping paper notes it is not.Editorial synthesis
    Editorial synthesis from general knowledge · primary document to be added to the ledger

Open questions and limitations

What is genuinely unknown, stated plainly. A missing field is not evidence that the outcome is safe, effective, or established.

  • The 372-patient Mexican phase 3 is unpublished; its safety data, including heart rate and blood pressure at 0.25 and 0.5 mg, exist only in the developer's summary.
  • No cardiovascular outcomes trial of tesofensine exists, and no trial has followed anyone beyond 24 weeks.
  • The COFEPRIS decision documents are not in the ledger; the regulatory timeline is from the developer's releases.

Questions people ask

What is tesofensine?

Tesofensine (NS-2330) is a small-molecule drug, not a peptide, that blocks the reuptake of serotonin, noradrenaline and dopamine at once. NeuroSearch developed it in Denmark for Alzheimer's and Parkinson's disease, where it failed, and noticed that patients lost weight. A 2008 phase 2 trial in 203 obese adults found about 9 to 10 percent placebo-adjusted weight loss at 0.5 to 1.0 mg a day over 24 weeks. Saniona and its Mexican partner Medix have since run a phase 3 and applied for approval in Mexico.

What is the half-life of tesofensine?

About ten days. Population pharmacokinetic modelling in Alzheimer's patients gave half-lives of 234 hours for tesofensine and 374 hours for its active metabolite M1, and the drug also recirculates through the bile. That is why once-daily tablets take weeks to reach a steady level, why effects and side effects build slowly, and why stopping does not clear it for a month or more.

What is Tesomet?

A fixed combination of tesofensine 0.5 mg with the beta-blocker metoprolol 50 mg, designed to blunt the heart-rate rise. In a 24-week randomized trial in 21 adults with hypothalamic obesity it did not change heart rate or blood pressure and reduced weight against placebo; sleep disturbance, dry mouth and headache were common, and one participant stopped after worsened anxiety.

Is tesofensine similar to phentermine?

In class, yes: both raise noradrenaline and dopamine signalling and both suppress appetite and raise heart rate. Tesofensine also blocks serotonin reuptake, has a half-life of about ten days against phentermine's day, and produced larger weight loss in its phase 2 trial than phentermine does alone. Phentermine is approved for short-term use; tesofensine is approved nowhere. No trial has compared them.

Is tesofensine a peptide?

No. It is a small synthetic molecule of the phenyltropane family, taken as a tablet, with no amino acids in it. Vendors list it beside peptides and label it one; the label describes the shop, not the drug.

How much weight do people lose on tesofensine?

In the one published obesity trial, 203 adults on diet lost 4.5%, 9.2% and 10.6% of body weight at 0.25, 0.5 and 1.0 mg daily over 24 weeks, against 2.0% on placebo. The developer reports about 10% at 24 weeks in its unpublished 372-patient Mexican phase 3 at 0.25 and 0.5 mg.

Is tesofensine approved anywhere?

Not as of the sources available on . Mexico's COFEPRIS gave a favourable non-binding opinion in February 2023, withheld approval in November 2024, and received a resubmitted dossier in 2025. It is not approved by FDA or EMA. A ranking page's claim of a 2023 Mexican approval is contradicted by the developer's own filings.

What are the side effects of tesofensine?

In the Tesomet trial: sleep disturbance in 50% versus 13% on placebo, dry mouth 43% versus 0%, headache 36% versus 0%, and one serious worsening of anxiety. In the phase 2, heart rate rose by up to about 8 beats a minute and blood pressure by 1 to 3 mmHg at the lower doses and more at 1.0 mg. Parkinson's trials saw more gastrointestinal and psychiatric events at higher doses.

Does tesofensine raise heart rate?

Yes, in the phase 2 obesity trial, by up to about 8 beats a minute at the doses carried into phase 3, and blood pressure rose at 1.0 mg. The Tesomet combination adds the beta-blocker metoprolol specifically to cancel this, and in its trial heart rate and blood pressure did not change.

What is the half-life of tesofensine?

About ten days: 234 hours for the drug and 374 hours for its active metabolite M1 in population modelling, with recirculation through the bile. Levels take four to six weeks to plateau and as long to clear.

Why did tesofensine fail in Parkinson's disease?

In 261 early patients, none of three doses improved the Parkinson's rating scale over 14 weeks. In advanced patients with fluctuations, 0.5 and 0.25 mg gave modest gains without a dose-response while adverse events rose with dose. Development in Parkinson's and Alzheimer's stopped; the weight loss seen in those patients became the new target.

How does tesofensine compare with semaglutide?

On weight, tesofensine's 24-week phase 2 result (about 9 to 10% placebo-adjusted) approaches what GLP-1 drugs achieve over a similar period, which is why it attracts interest as an oral option. On evidence, they are not comparable: semaglutide has cardiovascular outcome trials showing benefit; tesofensine has a heart-rate signal and no outcomes trial. No study has compared them directly.

Is tesofensine similar to sibutramine?

Closely. Both block noradrenaline and serotonin reuptake (tesofensine adds dopamine), both suppress appetite, both raise heart rate. Sibutramine was withdrawn in 2010 after the SCOUT trial found more cardiovascular events; tesofensine has never been tested in such a trial.

Is tesofensine banned in sport?

Yes, in competition: WADA classes it under S6 stimulants. Its ten-day half-life means a dose taken weeks before an event can still test positive.

Can tesofensine be injected?

It was infused intravenously only in pharmacokinetic studies of healthy volunteers. Every efficacy trial used tablets, and it is a tablet drug; 'injectable tesofensine' has no study behind it and no reason to exist.

What is Obexol?

A brand name that appears in searches alongside tesofensine and in connection with the Mexican application. The developer's public pipeline page names Tesomet (the metoprolol combination) and describes the monotherapy without a brand; no approved product under any name is documented in the sources available.

Sources

Full citations. Every claim above links to one of these by its id.

  1. 1
  2. 2
  3. 3
  4. 4
  5. 5
  6. 6
    Centrally Acting Agents for Obesity: Past, Present, and Future.
    pmid-30014268 · · peer-reviewed
  7. 7
  8. 8
    Safety of antiobesity drugs.
    pmid-25114779 · · peer-reviewed
  9. 9
    Anti-obesity drugs: a review about their effects and their safety.
    pmid-22439841 · · peer-reviewed
  10. 10
    Pharmacotherapies for obesity: past, current, and future therapies.
    pmid-21197148 · · peer-reviewed
  11. 11
    Pharmacological management of appetite expression in obesity.
    pmid-20234354 · · peer-reviewed
  12. 12
Show the remaining 11 sources
  1. 13
  2. 14
  3. 15
  4. 16
  5. 17
  6. 18
  7. 19
  8. 20
  9. 21
  10. 22
  11. 23

Reference card

Reference card · generated /compounds/tesofensine
Compound
Tesofensine, metabolic other
Evidence tier
Human clinical trial
Indexed publications
63 · 12 RCTs · 7 other clinical trials
Approval
not approved · max phase 2
Routes reported
intravenous, oral, subcutaneous
Reviewed
Adam Mirando, PharmD,

Study figures are as published in each source and are not recommendations. Print or save this card with its date.

Last reviewed and what changed

Newest first. These are the record's own revision dates, and the same dates feed the sitemap.

  1. · Reviewed by Adam Mirando, PharmD, on 2026-09-25.
  2. · Label correction: 1 evidence rows built from detection and doping-control papers carried study designs such as animal or in-vitro work. They are relabelled Analytical method, the label scripts/draft_claims.py has applied since the rule was added; these rows predate it. pmid-42320973 (Human study -> Analytical method)
  3. · Written under the sequencing rule after research/intents/tesofensine.json: guide (8 sections incl. a table of all human studies and a comparison with sibutramine), FAQ to 12 plus 9 from the map, hand-written dose, timeline and adverse-event claims with frequencies from the abstracts; mechanism (small molecule, not a peptide), reported-use and regulatory claims with the dated COFEPRIS timeline; a misdrafted interactions claim removed; intent-driven H1 and title. Triage: a misdrafted duration claim removed (a review's '12 months' referred to other drugs' phase 3 trials).
  4. · Claims drafted extractively from 23 ledger sources by scripts/draft_claims.py: 32 claims, 19 evidence-table rows. Status researched -> draft.
  5. · Claims drafted extractively from 23 ledger sources by scripts/draft_claims.py: 41 claims, 19 evidence-table rows. Status researched -> draft.
  6. · Metadata refreshed by scripts/fetch_evidence.py --refresh-meta: chembl None -> CHEMBL3989690.
  7. · Evidence fetched from Europe PMC and ChEMBL by scripts/fetch_evidence.py; claims not yet written.