This PACUPod episode reviews a secondary analysis of the SUMMIT trial investigating how baseline adiposity (BMI and central adiposity via waist-height ratio) and weight loss influence tirzepatide's benefits in obesity-related HFpEF. The discussion covers study design, primary outcome (time to cardiovascular death or worsening heart failure), and secondary outcomes (KCCQ-CSS, six-minute walk distance, CRP, body weight, and systolic blood pressure). Tirzepatide reduced the primary endpoint across all BMI and WHR tertiles, while improvements in functional and inflammatory markers varied with adiposity. Central adiposity identified higher-risk subgroups beyond BMI, and greater weight loss correlated with better 6MWD, quality of life, and reductions in CRP and SBP, suggesting weight loss mediates several benefits. The episode also discusses clinical implications, including targeting central adiposity, dosing considerations, potential pharmacologic interactions, and the need for longer-term data. Future directions include imaging studies to assess remodeling, combination therapy with other HFpEF agents, patient-reported outcomes, precision medicine for responder phenotyping, and cost-effectiveness analyses.