Recent FDA approvals have expanded the indication for semaglutide to include the reduction of major adverse cardiovascular events (MACE), such as heart attack, stroke, and cardiovascular death, in adults with established cardiovascular disease and obesity
However, there were no significant differences in HbA1c reductions between any of the cotadutide dose groups and the liraglutide (1.8 mg) group
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GLP-1R activation in the hypothalamus and brainstem suppresses appetite via POMC neuron stimulation and NPY/AgRP inhibition, slows gastric emptying, and potentiates glucose-dependent insulin secretion
This meant GLP-1 would need to be given in high doses if it was to have any therapeutic potential