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They just needed time to manifest. Fen-phen, a combination of fenfluramine and phentermine, was a popular diet drug in the 90s

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Moreover, the combined GLP-1 mechanisms of weight loss and delayed carbohydrate absorption may also be the key drivers of remission of type 2 diabetes and reduced cardiovascular events found by GLP-1 analogues

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It was demonstrated, that metabolic disturbances in hypothalamic astrocytes, caused either by selective knock-out of insulin receptors or decreased generation of reactive oxygen species (ROS) modulated glucose transport via BBB and also led to modification in behavioral responses in experimental animals [95, 96]