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Tesofensine is a serotonin-noradrenaline-dopamine reuptake inhibitor which was originally studied for its effect on Parkinson’s and Alzheimer’s. Unfortunately, its exploration for these indications were limited because the research subjects starting losing too much weight. Since then, tesofensine has been studied as a way to treat obesity via its ability to reduce appetite. This molecular compound indirectly stimulates the cholinergic system and showed to be more successful than other weight loss agents. Tesofensine (TE) increases transmission of 3 monoaminergic neurotransmitters in the brain. These neurotransmitters are serotonin, norepinephrine, and dopamine which help regulate energy balance and are linked to obesity and depression. On average, its 6-month weight loss results from a phase 2b clinical trial resulted in a weight loss of around 25 pounds. TE research has shown a pronounced effect on appetite sensations and a slight effect on energy expenditure. Both effects can contribute to the strong weight reducing effect.
Semaglutide is a derivative of the naturally occurring GLP-1, a peptide known to lower blood sugar levels and enhance insulin secretion. Research shows that Semaglutide may also improve heart, liver, and lung function while helping to slow or prevent the effects of Alzheimer’s disease. Semaglutide has been shown to significantly decrease appetite by delaying gastric emptying and reducing intestinal motility. Glucagon-Like Peptide-1 (GLP-1) Analog Shown to Stimulate Insulin and Suppress Glucagon Secretion in a Glucose-Dependent Manner.
John P.H. Wilding, D.M., Rachel L. Batterham, M.B., B.S., Ph.D., Salvatore Calanna, Ph.D., Melanie Davies, M.D., Luc F. Van Gaal, M.D., Ph.D., Ildiko Lingvay, M.D., M.P.H., M.S.C.S., Barbara M. McGowan, M.D., Ph.D., Julio Rosenstock, M.D., Marie T.D. Tran, M.D., Ph.D., Thomas A. Wadden, Ph.D., Sean Wharton, M.D., Pharm.D., Koutaro Yokote, M.D., Ph.D March 18, 2021 N Engl J Med 2021; 384:989-1002
M A Heffernan, A W Thorburn, B Fam, R Summers, B Conway-Campbell, M J Waters, F M Ng
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