Join JACC Editor in Chief Harlan Krumholz, MD, SM, as he speaks about this ACC.25 presentation published in JACC. This fascinating study by Rohan Khera et al independently analyzed patient-level data from the SURMOUNT trials of tirzepatide for obesity. The study revealed striking individual variability in weight loss and metabolic response, even to a highly effective therapy—an insight powerfully illustrated through waterfall plots. Reviewers praised the transparent, sponsor-independent approach and the study’s contribution to precision medicine, though they noted it was descriptive rather than predictive, underscoring the need for future research to identify what drives differential treatment response.