Tesofensine

Research overview

Key studies

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

   Randomized, double-blind, placebo-controlled phase 2, 24 weeks, 203 participants (NCT00394667)
   Model: Humans (adults with obesity, BMI 30 to 40)

   Mean weight loss was 4.5%, 9.2% and 10.6% with tesofensine 0.25, 0.5 and 1.0 mg versus 2.0% with placebo; dry mouth, nausea, constipation, diarrhoea and insomnia were most common; heart rate rose 7.4 bpm with 0.5 mg ^1. This report is subject to a 2013 expression of concern ^2.

2. Astrup et al., Obesity (pooled neurology trials) (2008)

   Meta-analysis of four randomized, double-blind trials, 14 weeks, 968 participants
   Model: Humans (patients with Parkinson's or Alzheimer's disease)

   Weight change was +0.5% with placebo and -0.5% to -2.8% across tesofensine doses; heart rate rose by up to 6.8 bpm with no effect on blood pressure ^4.

3. Rascol et al., Arch Neurol (ADVANS) (2008)

   Pilot phase 2, randomized, double-blind, placebo-controlled, 14 weeks (NCT00148512)
   Model: Humans (advanced Parkinson's disease with motor fluctuations)

   Modest improvements in UPDRS II+III at one dose and off-time at another, with no clear dose-response; gastrointestinal and neuropsychiatric adverse events were more frequent with tesofensine ^5.

4. Huynh et al., Eur J Endocrinol (Tesomet, hypothalamic obesity) (2022)

   Randomized, placebo-controlled, 24 weeks, 21 participants
   Model: Humans (adults with hypothalamic obesity)

   Additional weight change of -6.3% versus placebo; sleep disturbance (50% vs 13%), dry mouth (43% vs 0%) and headache (36% vs 0%); one treatment-related serious adverse event of exacerbated anxiety ^6.

5. Schoedel et al., Clin Pharmacol Ther (2010)

   Single-dose, randomized, double-blind crossover versus placebo, d-amphetamine, bupropion and atomoxetine
   Model: Humans (recreational stimulant users, n=52)

   Subjective effects of tesofensine did not differ from placebo and were lower than d-amphetamine on primary measures ^7.

Doses used in published trials

What investigators administered in the cited studies, recorded as a fact about those studies. Not a protocol and not a recommendation.

• In the phase 2 obesity trial (NCT00394667), after a 2-week run-in, 203 adults on an energy-restricted diet were randomized to tesofensine 0.25 mg, 0.5 mg or 1.0 mg, or placebo, once daily for 24 weeks ^1.
• In the four pooled Parkinson's and Alzheimer's trials, patients received oral tesofensine 0.125, 0.25, 0.5 or 1.0 mg or placebo once daily for 14 weeks without a weight-loss programme ^4.
• In ADVANS (NCT00148512), patients with advanced Parkinson's disease received tesofensine 0.125, 0.25, 0.5 or 1 mg or placebo tablets once daily for 14 weeks ^5.
• In the hypothalamic obesity trial, 21 adults were randomized to Tesomet (tesofensine 0.5 mg with metoprolol 50 mg) or placebo for 24 weeks with diet and lifestyle counselling ^6.
• In NCT02737891, 60 adults with type 2 diabetes received oral tesofensine 0.5 mg plus metoprolol 100 mg or matching placebo; outcomes were assessed from baseline to day 90 ^9.

Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

• Dry mouth, nausea, constipation, hard stools, diarrhoea, insomnia
  Most common adverse events (rates not given in the abstract)
  Phase 2 obesity trial, 24 weeks ¹ · Not graded in the abstract
• Heart-rate increase
  +7.4 bpm with 0.5 mg vs placebo at 24 weeks
  Phase 2 obesity trial ¹ · No significant blood-pressure increase at 0.25 and 0.5 mg
• Heart-rate increase
  +2.1 to +6.8 bpm across doses vs -0.4 placebo
  Pooled Parkinson's and Alzheimer's trials, 14 weeks ⁴ · No effect on blood pressure
• Sleep disturbances (with metoprolol)
  50% vs 13% placebo
  Hypothalamic obesity, 24 weeks ⁶ · Mostly mild
• Dry mouth (with metoprolol)
  43% vs 0% placebo
  Hypothalamic obesity, 24 weeks ⁶ · Mostly mild
• Headache (with metoprolol)
  36% vs 0% placebo
  Hypothalamic obesity, 24 weeks ⁶ · Mostly mild
• Gastrointestinal and neuropsychiatric adverse events
  More frequent than placebo, especially at higher doses
  Advanced Parkinson's disease, 14 weeks ⁵ · Not graded in the abstract

What is not known: No phase 3 results, regulatory approvals or long-term outcome data were confirmed in the allowed sources reviewed ^10. Adverse-event reporting from the main obesity trial is subject to a published expression of concern ^2,3. Cardiovascular safety over longer periods, psychiatric effects and effects of the very long half-life on cumulative exposure have not been established ^6,8.

Regulatory status

Status

Not approved by the FDA; an openFDA Drugs@FDA query returned no application record ^10. Phase 2 trials have been completed and registered on ClinicalTrials.gov, including Tesomet trials with posted results ^9. No phase 3 results or national approvals were confirmed in the allowed sources reviewed.

United States (FDA)

Not approved; an openFDA Drugs@FDA query for tesofensine returned no application record ^10. Tesofensine does not appear in any category of FDA's May 14, 2026 503A bulk drug substances list ^11.

Sport (WADA)

Prohibited in competition. Tesofensine is named in section S6.B, specified stimulants, of the WADA 2026 Prohibited List ^13.

Status varies by country and changes over time. How we describe regulatory status.

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. 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
3. Under-reporting of adverse effects of tesofensine Lancet. 2013
4. Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease Obesity (Silver Spring). 2008
5. Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study Arch Neurol. 2008
6. Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity Eur J Endocrinol. 2022
7. Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users Clin Pharmacol Ther. 2010
8. Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease Br J Clin Pharmacol. 2007
9. Safety and Efficacy Study of Tesofensine/Metoprolol Treatment in Subjects With Type 2 Diabetes Mellitus (NCT02737891), registry record with posted results ClinicalTrials.gov. 2017
10. Drugs@FDA application data queried through openFDA for tesofensine (no matching application record returned on 23 October 2026) openFDA / Drugs@FDA. 2026
11. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (categories 1, 2 and 3; updated May 14, 2026) FDA. 2026
12. PubChem compound record for tesofensine (CID 11370864; CAS 195875-84-4) PubChem. 2026
13. International Standard: Prohibited List 2026 World Anti-Doping Agency. 2026