Semaglutide significantly improves HFpEF outcomes in obese patients, with STEP HFpEF (n = 529) and STEP HFpEF DM (n = 616) demonstrating Kansas City Cardiomyopathy Questionnaire Clinical Summary Score increases of 16.6 and 13.7 points (vs. 8.7 and 6.4 with placebo, P < 0.001), weight reductions of 13.3% and 9.8% (P < 0.001), and 43.5% C-reactive protein reductions (P < 0.001), all of which are clinically relevant in HFpEF management. The gene discussed is CRP; the disease is diabetes mellitus.