The advent of therapies targeting glucagon-like peptide1 receptor agonists (GLP-1 RA), such as semaglutide, and di- and triagonists, like tirzepatide and retatrutide, marks a breakthrough in obesity treatment and is poised to revolutionize health care. Due to their significantly improved efficacy compared with older-generation antiobesity medications in terms of 1- and 2-year weight loss,1 they have gained exceptional popularity. However, several questions remain regarding how clinicians should integrate these medications into clinical practice. Key considerations include delineating ideal treatment objectives, establishing criteria for nonresponse, and formulating strategies for combination therapy protocols.