Tesofensine

Metabolic / Fat Loss

Also known as: NS2330, Tesomet

Monoamine Reuptake InhibitorsResearch phase: Phase 3Regulatory: Not FDA-approved. Phase 3 clinical trials in progress. Available through compounding pharmacies in some markets.

Mechanism

Tesofensine is a triple monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine) originally developed for Parkinson's and Alzheimer's that was repurposed for obesity after Phase 2 trials showed dramatic weight loss — averaging 12.8 kg over 6 months at the highest dose, making it one of the most potent oral weight loss agents ever tested. It is in Phase 3 trials for obesity.

Technical detail

Tesofensine (NS2330) is a novel triple monoamine reuptake inhibitor that blocks the presynaptic reuptake of serotonin (SERT), norepinephrine (NET), and dopamine (DAT) transporters, increasing synaptic concentrations of all three monoamines. This produces potent appetite suppression via hypothalamic serotonergic and noradrenergic satiety pathways, increased thermogenesis via sympathetic activation, and enhanced reward from eating (reducing hedonic overconsumption) via dopaminergic modulation. Phase 2 TIPO-1 trial showed dose-dependent weight loss of 6.7-12.8 kg over 24 weeks. Phase 3 trials (Saniona) are ongoing for obesity with and without type 2 diabetes.

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