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However, its future trajectory is far from linear as many uncertainties remain, e.g., acceptance of obesity as a chronic disease, budget impact faced by payers and health systems willingness and ability to pay, the readout of further cardiovascular outcomes trials after the high profile results of 2023s SELECT trial for Wegovy, or new entrants challenging first generation therapies with alternative mechanisms of action (MoA) to address shortcomings such as gastrointestinal tolerability, current drugs being injectables, or the durability and quality of weight loss which distinguishes between fat and lean body mass

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Here, the authors assess the molecular mechanisms of peptide agonists binding to GLP-1R and the responses elucidated by these ligands, including distinct kinetics of G protein activation.

Purpose of Review This review summarizes the current understanding of the physiologic influence of GLP-1 RAs on gastrointestinal motility, highlights key clinical implications of these effects, and defines areas for future investigation

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