Monoamine reuptake inhibitor

Tesofensine is not a GLP-1 anything. It is a triple monoamine reuptake inhibitor - it blocks the transporters for noradrenaline, dopamine and serotonin - originally developed for Parkinson's and Alzheimer's disease, where trials failed but participants lost weight. That observation led to a phase 2 obesity trial in 203 patients: 24 weeks at 0.5 mg gave 9.2% weight loss against 2.0% on placebo, with heart rate up 7.4 beats per minute. It never reached phase 3 for obesity. That trial also carries a Lancet expression of concern, issued in 2013 over under-reporting of adverse effects and never withdrawn. A newer formulation combining tesofensine with metoprolol has been tested in hypothalamic obesity, a condition with almost no other options, giving 6.3% more weight loss than placebo in 21 patients.