What it is
Tesofensine is an oral serotonin-noradrenaline-dopamine reuptake inhibitor investigated for obesity. It is not a peptide but a small molecule, and it works on brain chemistry rather than on gut hormones. In human trials it produced appetite-suppressing weight loss.
In the PeptidesAI encyclopedia, tesofensine is categorized under weight management. Its development for obesity has been ongoing and uncertain, and it is not approved by the FDA.
How it's thought to work
Tesofensine is an inhibitor of the presynaptic uptake (reuptake) of serotonin, noradrenaline and dopamine, three signalling chemicals in the brain; blocking reuptake increases their signaling, which is how it is thought to suppress appetite. This is a centrally acting mechanism distinct from GLP-1 agonists. In mice, tesofensine inhibited a subset of GABAergic neurons in the lateral hypothalamus, reducing their ability to promote feeding behavior.
What the research says
A phase 2 randomized trial in 203 obese patients in Denmark reported that, after 24 weeks, the two higher tesofensine dose groups lost 9.2% and 10.6% of body weight more than the diet-and-placebo group, whose weight loss was 2.0%. The authors noted that these findings needed confirmation in phase 3 trials.
A small randomized trial of Tesomet, a combination of tesofensine and metoprolol, in 21 adults with hypothalamic obesity (obesity after injury to the hypothalamus, a brain region involved in appetite) reported an additional mean weight change of -6.3% versus placebo over 24 weeks.
Development for obesity has been ongoing and uncertain. Tesofensine is not FDA-approved.
Reported side effects
In the phase 2 trial, the most common adverse events were dry mouth, nausea, constipation, hard stools, diarrhea and insomnia, and heart rate rose in one dose group, while blood pressure did not differ significantly from placebo in the two lower-dose groups. Mood changes are also listed as a reported effect. In the small Tesomet trial, one patient stopped treatment because of a treatment-related serious adverse event of worsened pre-existing anxiety.
Form
Tesofensine is taken by mouth as tablets or capsules, so it is not reconstituted.
Important notes
Tesofensine is not FDA-approved. Material sold as a research chemical is not a regulated product, and its quality and purity are not independently verified.
Sources
- Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial.. Astrup A et al. Lancet, 2008. Human trial
- Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity.. Huynh K et al. Eur J Endocrinol, 2022. Human trial
- Tesofensine, a novel antiobesity drug, silences GABAergic hypothalamic neurons.. Perez CI et al. PLoS One, 2024. Preclinical
Frequently asked questions
These questions cover the same ground as the sections above, in a shorter format.
What is tesofensine?
An oral serotonin-noradrenaline-dopamine reuptake inhibitor (not a peptide) investigated for obesity. It is not FDA-approved.
How is tesofensine thought to work?
It blocks reuptake of serotonin, noradrenaline and dopamine, increasing their signaling, which is thought to suppress appetite through a centrally acting mechanism distinct from GLP-1 agonists.
What does the research on tesofensine say?
A phase 2 randomized trial reported weight loss 9.2% and 10.6% greater than diet and placebo at the two higher doses after 24 weeks, with the authors calling for phase 3 confirmation.
What are the reported side effects of tesofensine?
Dry mouth, nausea, constipation, diarrhea and insomnia were most common in the phase 2 trial, and heart rate rose in one dose group. Mood changes are also listed.
The full entry, plus the calculator
The PeptidesAI app has the complete encyclopedia entry for Tesofensine — one of 70 compounds covered — plus the reconstitution calculator, a dose log and reminders. Free to download on iPhone.
Download on the App Store