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Studies in mice with CNS neuron-specific GLP-1R knockout showed that liraglutide failed to induce weight loss but still improved glucose levels, suggesting that brain GLP-1Rs are necessary for the weight-lowering effect of GLP-1RAs but not essential for their glucose-lowering effects ( Notably, the amount of incretin mimetics entering the brain parenchyma does not correlate with their efficacy in weight reduction ( In the brain, the two incretins are not redundant and may complement each other in regulating orexigenic and anorexigenic pathways ( 5.3 GIP and GLP-1 effects on gastric emptying The secretion of endogenous GIP does not correlate with gastric half-emptying times ( Figure 1 Section D)

And they werent wrong

However, real-world practice does have hurdles

Chang L, et al

HR 0.83
