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AMIRAVOResearch Library

Tesofensine vs semaglutide

Tesofensine and semaglutide are very different drugs that have both been studied for obesity: tesofensine is a small molecule that blocks the reuptake of noradrenaline, dopamine and serotonin, whereas semaglutide is a peptide GLP-1 receptor agonist 1,2,3. Semaglutide is FDA-approved, while tesofensine's highest registered phase is phase 2 and no Drugs@FDA record was returned on 24 October 2026 4,5,6. No trial comparing them was identified 7.

Unbranded reference vial illustrating Tesofensine; not an actual product
Tesofensine
Investigational
Unbranded reference vial illustrating Semaglutide; not an actual product
Semaglutide
FDA-approved

Side by side

FieldTesofensineSemaglutide
ClassSmall molecule (not a peptide); triple monoamine reuptake inhibitor 1,2Peptide GLP-1 receptor agonist 3
Origin and structureSynthetic small molecule, formula C17H23Cl2NO 2GLP-1 analogue with 94% homology to human GLP-1 and a C18 fatty diacid at lysine 26 3
Proposed mechanismInhibits presynaptic reuptake of noradrenaline, dopamine and serotonin 1Activates the GLP-1 receptor, a regulator of appetite and calorie intake 3
Half-lifeAbout 234 hours (major metabolite M1 about 374 hours) in a population model of patients with Alzheimer's disease 8About 1 week per the FDA labels 3,9
Highest human trial phasePhase 2 (highest phase in registry records) 1,5Approved; phase 3 and outcome trials published 10,11
FDA statusNot approved; no Drugs@FDA record as of 24 October 2026 6; not listed on FDA's 503A bulk nominations list updated 14 May 2026 12Approved as Ozempic (5 December 2017) and Wegovy (4 June 2021), per Drugs@FDA as of 24 October 2026 4
Published human outcomes2008 phase 2 trial (203 adults with obesity): body-weight change of -4.5% to -10.6% vs -2.0% with diet and placebo at 24 weeks 1; the journal later published an expression of concern about this trial 13STEP 1: -14.9% vs -2.4% at 68 weeks 10; SELECT: cardiovascular events hazard ratio 0.80 11
Safety signalsDry mouth, nausea, constipation, diarrhoea and insomnia; heart rate rose by 7.4 beats per minute in one dose group 1; a published letter raised under-reporting of adverse effects 14Boxed warning for thyroid C-cell tumours seen in rodents; gastrointestinal reactions most common; heart-rate increase listed in warnings 3
WADA statusNamed in S6.B (specified stimulants); prohibited in competition 15Not named on the 2026 Prohibited List 15; GLP-1 receptor agonist status unchanged for 2027 16
Who funded the evidenceRegistry sponsors include NeuroSearch, Boehringer Ingelheim and Saniona 5Novo Nordisk 10,11

Tesofensine: what the data says

Tesofensine was first studied in Parkinson's and Alzheimer's disease before being studied for obesity 1,17.

  • In a 24-week phase 2 trial in five Danish obesity centres (203 adults; human data), mean body-weight change with diet was -4.5%, -9.2% and -10.6% across three doses vs -2.0% with diet and placebo 1. The Lancet published an expression of concern about this trial in 2013 13.
  • In a pooled analysis of four 14-week Parkinson's and Alzheimer's trials (968 patients; human data), the placebo-subtracted body-weight change was about 4%, with dose-related heart-rate increases 17.
  • In 21 adults with hypothalamic obesity (human data), tesofensine combined with metoprolol (Tesomet) produced a placebo-adjusted change of -6.3% over 24 weeks; sleep disturbance and dry mouth were common 18.
  • In recreational stimulant users (human data), single-dose subjective effects did not differ from placebo 19.

Semaglutide: what the data says

Semaglutide is FDA-approved for type 2 diabetes, cardiovascular and kidney risk reduction in specified groups, chronic weight management and, under accelerated approval, MASH with moderate to advanced fibrosis 3,9.

  • In STEP 1 (1961 adults; human data), body-weight change at 68 weeks was -14.9% vs -2.4% with placebo 10.
  • In SELECT (17,604 adults with cardiovascular disease; human data), the primary cardiovascular outcome occurred in 6.5% vs 8.0% with placebo 11.

Key research differences

  • Drug type and target: tesofensine is a small-molecule monoamine reuptake inhibitor acting on brain neurotransmitters, whereas semaglutide is a peptide hormone analogue acting on the GLP-1 receptor 1,3.
  • Regulatory status: semaglutide is FDA-approved; tesofensine had no Drugs@FDA record on 24 October 2026 and its registered trials reach phase 2 4,5,6.
  • Anti-doping: tesofensine is a specified stimulant prohibited in competition (S6.B), while semaglutide is not named on the 2026 List 15.
  • Evidence quality: the main tesofensine obesity trial is the subject of a journal expression of concern, whereas semaglutide has large phase 3 and outcome trials 10,11,13.
  • Half-life: about 234 hours for tesofensine in a population model of Alzheimer's patients vs about 1 week for semaglutide per its labels 3,8.

Where the evidence is limited

No trial comparing tesofensine with semaglutide was identified 7. Tesofensine's obesity data come from a single 24-week phase 2 trial with a later expression of concern, pooled neurology trials and a small trial of a combination product, whereas semaglutide's data come from 68-week and longer phase 3 trials, so the results cannot be ranked 1,10,13,17,18.

Frequently asked questions

Does tesofensine lead to more body-weight change than semaglutide?
This cannot be determined. They have not been compared in a trial, and tesofensine's obesity evidence is limited to phase 2 studies, one of which carries a journal expression of concern 1,7,13.
Is tesofensine a peptide or a GLP-1 drug?
No. Tesofensine is a small molecule that inhibits reuptake of noradrenaline, dopamine and serotonin; it does not act on the GLP-1 receptor as semaglutide does 1,2,3.
Is tesofensine FDA-approved?
No. An openFDA query of Drugs@FDA on 24 October 2026 returned no application record for tesofensine 6.
Is tesofensine banned in sport?
Yes, in competition. WADA's 2026 Prohibited List names tesofensine among the specified stimulants in section S6.B 15.

References

  1. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial Lancet. 2008
  2. PubChem compound record for tesofensine (CID 11370864): molecular formula C17H23Cl2NO PubChem. 2026
  3. WEGOVY (semaglutide) injection and tablets: prescribing information, DailyMed set ID ee06186f-2aa3-4990-a760-757579d8f77b (label version dated 18 June 2026) FDA label (via openFDA). 2026
  4. Drugs@FDA application records for NDA 215866 (Mounjaro), NDA 217806 (Zepbound), NDA 209637 (Ozempic), NDA 215256 (Wegovy), NDA 022341 (Victoza) and NDA 206321 (Saxenda): original approval dates (queried 24 October 2026) Drugs@FDA (via openFDA). 2026
  5. ClinicalTrials.gov registry search for tesofensine as intervention (13 records; highest listed phase 2; retrieved 24 October 2026) ClinicalTrials.gov. 2026
  6. Drugs@FDA application data queried through openFDA for tesofensine (no matching application record returned on 24 October 2026) openFDA / Drugs@FDA. 2026
  7. ClinicalTrials.gov registry search for tesofensine AND semaglutide as interventions (0 records; retrieved 24 October 2026) ClinicalTrials.gov. 2026
  8. Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease Br J Clin Pharmacol. 2007
  9. OZEMPIC (semaglutide) injection: prescribing information, DailyMed set ID adec4fd2-6858-4c99-91d4-531f5f2a2d79 (label version dated 1 June 2026) FDA label (via openFDA). 2026
  10. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) N Engl J Med. 2021
  11. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) N Engl J Med. 2023
  12. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (updated May 14, 2026) FDA. 2026
  13. Expression of concern--effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial Lancet. 2013
  14. Under-reporting of adverse effects of tesofensine Lancet. 2013
  15. The 2026 Prohibited List - World Anti-Doping Code, as published in the Netherlands Treaty Series (Tractatenblad 2026, 25; Council of Europe Anti-Doping Convention appendix, in force 1 January 2026) Tractatenblad (Official Publications of the Kingdom of the Netherlands). 2026
  16. WADA publishes 2027 Prohibited List (news release, 21 September 2026) World Anti-Doping Agency. 2026
  17. Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease Obesity (Silver Spring). 2008
  18. Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity Eur J Endocrinol. 2022
  19. Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users Clin Pharmacol Ther. 2010

For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page compares published research and is not medical advice or a recommendation.