Tesofensine

Overview

Tesofensine is a small-molecule triple monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine) — NOT a peptide. Originally developed by NeuroSearch for Parkinson's and Alzheimer's disease (which it failed to benefit) and repositioned for obesity by Saniona. Not FDA-approved in the US.

Mechanism of Action

Inhibits presynaptic reuptake of serotonin, norepinephrine, and dopamine, elevating synaptic monoamine tone. Appetite suppression and modestly increased energy expenditure are driven primarily by noradrenergic and dopaminergic signaling in hypothalamic and reward circuits.

Research Summary

Pivotal Phase 2 (Astrup et al., Lancet 2008, n=203, 24 weeks, Denmark) showed placebo-subtracted weight loss of 4.5%, 9.2%, and 10.6% at 0.25, 0.5, and 1.0 mg/day — roughly twice orlistat at 0.5 mg. (The Lancet issued an expression of concern about that trial in 2013.) Saniona's Mexico partner Medix ran a Phase 3 registration study that met its primary endpoint; Medix filed with COFEPRIS in May 2023 with supplemental data submitted in 2024. As of April 2026 a final Mexican approval decision is still pending — the commonly repeated '2022 Mexico approval' claim is inaccurate. Tesomet (tesofensine + metoprolol, intended to blunt cardiovascular signal) is in development for hypothalamic obesity and Prader-Willi syndrome.

Dosing Information

Reported Side Effects

• Nausea
• Constipation
• Dry mouth
• Insomnia
• Anxiety / mood change
• Elevated heart rate
• Elevated blood pressure

Research References

• Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients — Astrup et al., Lancet (2008)
• Tesofensine pipeline page (mechanism, development status, Medix/Mexico partnership) (2026)
• Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity (Huynh et al.) (2022)