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It is produced by vitamin D3 but requires vitamin K2 to be activated

In preclinical efficacy studies in diet-induced obese (DIO) mice and obese monkeys, treatment with AMG133 reduces body weight and improves metabolic parameters to a larger extent than a GLP-1 receptor agonist alone (50)

Respirology 18 , 313322 (2013)

32,33 Under physiological conditions, besides the paracrine secretion pathway in the gastrointestinal tract, most endogenous GLP-1 in circulation is locally deactivated by DPP-4 and the liver, 34 making it difficult to directly enter the CNS through the blood-brain barrier

Together, they would target five distinct metabolic pathways simultaneously