Tesofensine

NS2330 · Tesomet (with metformin)

Weight LossInvestigationalPhase IIResearchOral

Popular for:Weight loss, triple monoamine reuptake inhibitor, appetite suppression

13

Registered Trials

11

Trial Publications

51

PubMed References

Phase II

Evidence Level

Overview

Tesofensine is a serotonin-noradrenaline-dopamine reuptake inhibitor (SNDRI) originally developed by NeuroSearch for Parkinson's disease and Alzheimer's. The short version: people usually care about it for weight loss, triple monoamine reuptake inhibitor, appetite suppression, but the strength of the evidence depends heavily on indication and study type.

Tesofensine is a serotonin-noradrenaline-dopamine reuptake inhibitor (SNDRI) originally developed by NeuroSearch for Parkinson's disease and Alzheimer's. During neurological trials, researchers noticed significant weight loss as a side effect, pivoting the drug toward obesity treatment.

Phase II trials showed remarkable results: up to 12.8% body weight loss over 6 months at the 1.0 mg dose — more than double most approved obesity drugs at the time. It works through a completely different mechanism than GLP-1 agonists, reducing appetite and increasing satiety through triple monoamine reuptake inhibition rather than gut hormone signaling.

Research Snapshot

What the evidence says

Phase II

Tesofensine currently shows 13 registered trials from ClinicalTrials.gov, 11 PubMed trial publications (11 RCT-tagged), and 51 PubMed references matching the stored source query. Treat PubMed references as literature surface area, not a count of clinical trials.

Known vs uncertain

Known signals

  • 13 registered trials are tracked from ClinicalTrials.gov intervention records.
  • 11 PubMed clinical-trial publications are indexed.
  • 11 PubMed randomized controlled trial publications are indexed.
  • 51 PubMed references are tracked separately from trial counts and can include animal, in-vitro, review, mechanism, or clinical records.

Open questions

  • Evidence strength may vary by indication, route, formulation, and population.
  • Public anecdotes can highlight interest or concern but do not establish clinical efficacy.
  • Regulatory status and compounding access can change independently from the research literature.

Mechanism of Action

Tesofensine inhibits the reuptake of serotonin, norepinephrine, and dopamine — the three major monoamine neurotransmitters involved in appetite regulation and reward.

Key Research Benefits

Up to 12.8% weight loss in Phase II (6 months)
Oral administration — pill form, no injection
Novel mechanism — not GLP-1 based, could be complementary
Works through appetite suppression and satiety enhancement
Being developed as Tesomet (tesofensine + metformin combination)

Clinical Evidence Summary

Research Pipeline

Preclinical
Animal
Phase I
Phase II
Phase III
Approved

13

Registered Trials

11

Trial Publications

11

RCT Publications

51

PubMed References

ClinicalTrials.govPubMed ESearchExact-name queryChecked May 3, 2026

Registered trials are ClinicalTrials.gov intervention records. Trial publications are PubMed records tagged as clinical trials or randomized controlled trials. PubMed references are broader source-query matches and can include animal studies, in-vitro work, reviews, mechanism papers, and trial publications.

13

Registered trials

11

Trial publications

11

RCT publications

51

PubMed references

17

Reviews

1

Meta-analyses

Registered trials source

Jun 1, 2026

Tesofensine

Uses the exact compound name as a ClinicalTrials.gov intervention query.

View source

Publication counts source

May 3, 2026

Tesofensine

Uses the exact display name.

View source

Investigational — Phase III (Saniona). Tesomet (combo with metformin) in trials for Prader-Willi syndrome and hypothalamic obesity. Not yet FDA-approved. Cardiovascular safety is the key regulatory hurdle.

Key PubMed References

51 PubMed references · showing top 25 by relevance

View all on PubMed

Structural basis for pharmacotherapeutic action of triple reuptake inhibitors.

Human Study

Li Y, Meng Y, Li N, et al. · Nature communications · 2025

PMID: 41392177

Tesofensine, a novel antiobesity drug, silences GABAergic hypothalamic neurons.

Animal Study

Perez CI, Luis-Islas J, Lopez A, et al. · PloS one · 2024

PMID: 38656972

New and emerging drug molecules against obesity.

Review

George M, Rajaram M, Shanmugam E · Journal of cardiovascular pharmacology and therapeutics · 2014

PMID: 24064009

Anti-hypertensive treatment preserves appetite suppression while preventing cardiovascular adverse effects of tesofensine in rats.

Animal Study

Bentzen BH, Grunnet M, Hyveled-Nielsen L, et al. · Obesity (Silver Spring, Md.) · 2013

PMID: 23784901

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.

Human Study

Lancet (London, England) · 2013

PMID: 23561987

Anecdotes & Sentiment

Public discussion, not clinical evidence

This section summarizes what people are talking about in public sources. It can be useful for spotting questions, hype cycles, and recurring concerns, but it is separate from the evidence sections above.

No curated public-discussion themes are live for Tesofensine yet.

Side Effects & Safety

- Increased heart rate (5-8 bpm in trials) - Dry mouth - Insomnia - Constipation - Potential for cardiovascular effects (main regulatory concern) - Not a benign compound — CNS-active, affects multiple neurotransmitter systems

Increased heart rate (5-8 bpm in trials)
Dry mouth
Insomnia
Constipation
Potential for cardiovascular effects (main regulatory concern)
Not a benign compound — CNS-active, affects multiple neurotransmitter systems

Known Interactions

No curated interaction entry is live for Tesofensine yet.

Until the interaction table is fully populated, use the interaction checker and related peptides below to explore adjacent compounds and likely research pairings.

Comparison Pages

Comparison pages

All

No comparison page is linked yet.

Frequently Asked Questions

Research Disclaimer

This page is for research and educational purposes only. The information presented is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Regulatory status can vary by compound, formulation, indication, and jurisdiction. Check official labeling, registry records, and qualified professional guidance before making any health-related decision. The studies referenced are linked to their original PubMed sources for verification.