Tesofensine: research

An oral appetite drug with weight-loss trial results and heart-rate and psychiatric risks.

Also called: NS2330, NS-2330, NS 2330.

Fat-loss drugs · Serotonin, norepinephrine and dopamine reuptake inhibitor.

At least 22 distinct human studies identified. The sponsor reports 34 development trials; many lack public detail. Phase 3 registry results exist; long-term safety is unsettled.

Studies

Tesofensine dosage

Typical reported dose: 0.5 mg by mouth once a day

  • TIPO-1: 0.25 mg: 0.25 mg daily once daily, by mouth. Studied in a trial. Studied in: Adults with obesity. (source)
  • TIPO-1: 0.5 mg: 0.5 mg daily once daily, by mouth. Studied in a trial. Studied in: Adults with obesity. (source)
  • TIPO-1: 1 mg: 1 mg daily once daily, by mouth. Studied in a trial. Studied in: Adults with obesity. (source)
  • Mexico phase 3: 0.25 mg: 0.25 mg daily once daily, by mouth. Studied in a trial. Studied in: Adults with obesity. (source)
  • Mexico phase 3: 0.5 mg: 0.5 mg daily once daily, by mouth. Studied in a trial. Studied in: Adults with obesity. (source)
  • Two-week energy study: 2 mg daily, days 1–7, then 1 mg daily, days 8–14 once daily, by mouth. Studied in a trial. Studied in: Overweight or moderately obese men. (source)

These are doses reported in labels, trials or user reports, not a personal plan. Check the source behind each one.

Work out syringe units with the dosing calculator

Tesofensine side effects and risks

Reported side effects

  • Dry mouth: Originally reported at 0.5 mg: 42.0% versus 11.5% placebo. Safety events were later found under reported., moderate (source)
  • Nausea: Originally reported at 0.5 mg: 20.0% versus 9.6% placebo., moderate (source)
  • Insomnia: Originally reported at 0.5 mg: 12.0% versus 1.9% placebo., moderate (source)
  • Hard stools: Originally reported at 0.5 mg: 14.0% versus 3.8% placebo., moderate (source)
  • Constipation: Originally reported at 1 mg: 16.3%; 0.5 mg: 2.0%; placebo: 7.7%. Frequency varies with dose., moderate (source)
  • Diarrhea: Originally reported at 0.5 mg: 8.0% versus 5.8% placebo., moderate (source)
  • Headache: Originally reported at 0.5 mg: 34.0% versus 40.4% placebo., moderate (source)
  • Dizziness: Originally reported at 0.5 mg: 10.0% versus 3.8% placebo., moderate (source)
  • Vomiting: Originally reported at 0.5 mg: 6.0% versus 1.9% placebo., moderate (source)
  • Raised heart rate or palpitations: 0.5 mg increased mean heart rate by 7.4 beats/min versus placebo. Palpitations were reported., serious (source)
  • High blood pressure: 1 mg increased blood pressure in TIPO 1; individual risk cannot be estimated reliably., serious (source)
  • Anxiety, mania, depression or unusual behavior: Serious psychiatric events occurred in small Tesomet studies. A population rate is unknown., serious (source)

Stop and get help if

  • Chest pain, fainting or a racing/irregular heartbeat: Stop exposure and get urgent medical care.
  • Fever with confusion, sweating, shaking or muscle twitching: Seek emergency care for possible serotonin toxicity.
  • Hallucinations, mania, severe agitation or suicidal thoughts: Stop exposure and seek urgent assessment; immediate danger needs emergency care.
  • Swollen tongue or throat, or trouble breathing: Seek emergency care for a possible severe allergic reaction.
  • Confusion, severe headache or seizures while taking desmopressin: Seek urgent care; low blood sodium is possible.
  • Persistent low glucose, confusion or inability to swallow safely: Use the prescribed hypoglycemia plan and seek urgent care.

Who should avoid it

  • pregnant: Pregnancy was excluded from obesity trials; fetal safety has not been established.
  • breastfeeding: Breastfeeding was excluded; milk transfer and infant safety are unknown.
  • tryingToConceive: Trials required contraception. No evidence-based preconception washout is established.
  • under18: General obesity dosing is not established under 18. A small PWS trial does not validate general pediatric use.
  • eatingDisorderHistory: Appetite suppression can worsen restrictive eating; obesity trials excluded eating disorders.
  • heartCondition: Heart rate can rise. Trials excluded major heart disease, arrhythmias and recent heart attack or stroke.
  • uncontrolledBloodPressure: Tesofensine can raise blood pressure; uncontrolled hypertension was excluded from trials.
  • psychiatricCondition: Anxiety, mania, paranoia and mood changes occurred. Bipolar illness or psychosis requires particular review.
  • depressionOrSuicidalThoughts: Trials screened mood and suicidality; serious depression was reported in a short Tesomet study.
  • kidneyDisease: Kidney function affected modeled exposure; significant impairment was excluded. No validated dose adjustment exists.
  • liverDisease: Significant liver disease was excluded; metabolism involves CYP3A4. No validated adjustment is available.
  • seizureDisorder: Epilepsy was excluded from TIPO-1; seizure risk has not been defined.
  • diabetes: Reduced intake may change glucose medicine needs. Diabetes trials used additional glucose monitoring.
  • other: Known allergy to tesofensine or its tablet ingredients should stop use.
  • other: Uncontrolled thyroid disease was excluded; it may compound heart-rate and weight effects.
  • other: Uncontrolled glaucoma and significant eye disease were excluded from the obesity trial.
  • surgeryPlanned: Tell the anesthesia team about exposure; the drug clears over weeks. No validated stop interval was found.
  • testedAthlete: Tesofensine is named in WADA 2026 S6.B and prohibited in competition.
  • other: Metoprolol protocols only: the label blocks severe bradycardia. TM005 also excluded resting heart rate <50 beats/min.
  • other: Metoprolol protocols only: the label contraindicates metoprolol with second- or third-degree heart block.
  • other: Metoprolol protocols only: sick sinus syndrome is a label contraindication unless a permanent pacemaker is in place.
  • other: Metoprolol protocols only: the label contraindicates metoprolol during cardiogenic shock.
  • other: Metoprolol protocols only: the label blocks use in decompensated heart failure. TM005 also excluded this condition.
  • other: Metoprolol protocols only: allergy to metoprolol or any component of its tablet is a label contraindication and a TM005 exclusion.

Interactions

  • MAO inhibitors: Avoid combining monoamine reuptake blockade with MAO inhibition: predicted serotonin toxicity or dangerous blood-pressure changes. MAOIs were excluded.
  • Serotonergic medicines and supplements: Predicted serotonin-toxicity risk; SSRIs/SNRIs were prohibited in Tesomet trials. Direct interaction rates are unknown.
  • Stimulants and other appetite suppressants: Overlapping stimulant effects may worsen heart rate, pressure, anxiety and sleep. Other appetite suppressants were excluded from trials.
  • Strong CYP3A4 inhibitors: Itraconazole increased exposure; effects with other strong CYP3A4 inhibitors are predicted, not directly measured.
  • Insulin and sulfonylureas: Reduced food intake and weight loss can lower glucose medicine needs. Hypoglycemia risk is inferred; combination data are limited.
  • Metoprolol and other beta blockers: Metoprolol was studied with tesofensine. It can slow the heart or lower pressure; it does not remove psychiatric risk.
  • Desmopressin: The trial protocol flags possible additive water retention and low sodium. The interaction is theoretical.
  • GLP-1 drugs and experimental appetite drugs: Formal stack trials are lacking. Reduced intake, nausea and heart-rate effects may overlap; community results cannot establish safety.

Product quality risks

  • A 2026 study measured 483 mcg in one capsule labeled 500 mcg. One product cannot establish market-wide quality.
  • No independent market-wide tesofensine purity, contamination or counterfeit survey was located.
  • FDA documented manufacturing-quality failures at an API distributor and identified tesofensine as ineligible for 503A compounding.
  • Oral product purity does not establish sterility or safety for injection.

How Tesofensine works

It blocks the pumps that clear serotonin, norepinephrine and dopamine between nerve cells. This can reduce hunger and change mood, sleep and heart rate. It does not work through the GLP-1 pathway.

  • Serotonin transporter (SERT): Blocks serotonin reuptake.
  • Norepinephrine transporter (NET): Blocks norepinephrine reuptake; may increase heart rate and blood pressure.
  • Dopamine transporter (DAT): Blocks dopamine reuptake; human brain scans show transporter occupancy.

Half-life: About 234 hours in an Alzheimer’s population model; active metabolite M1 about 374 hours.

Gaps: Mexico: the 2023 opinion was non-binding. The August 2026 sponsor report still describes an application; no final COFEPRIS authorization was confirmed. The 2008 obesity trial has a 2013 expression of concern; full corrected arm-level adverse-event rates were not recovered. Phase 3 results are public in registries, but no peer-reviewed Mexican results paper or complete safety table was found. At least 22 distinct exposed human studies were identified; sponsor-reported 34 development trials could not all be independently reconstructed. No long-term cardiovascular outcome trial establishes heart attack, stroke, valve or mortality risk. No established pregnancy, breastfeeding, fertility or preconception washout data. No validated chronic schedule above 1 mg/day, cycling schedule, taper or community stack protocol. The seven-day 2 mg loading study and 1/6/9 mg single-dose study are not chronic-dose evidence. No human subcutaneous or sublingual dose study found. Oral liquid stability and home preparation are unverified. Community prevalence labels describe only the retrieved discussions; no representative survey or verified product identity. Clinical-practice dosing from a non-selling clinician publication was not located. There are no FDA/EMA label protocols. The 2021 Tesomet orphan designations are not FDA marketing approvals; some reviews confuse these. Planned phase 2b Tesomet studies NCT05147415 and NCT05198362 withdrew with zero enrollment; they provide no human outcome data.

Related to Tesofensine

Tesofensine: the short version

Sources

Sources checked: 2026-10-18.

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