In the SUMMIT trial (Efficacy and Safety of Tirzepatide Versus Placebo in Patients With Heart Failure With Preserved Ejection Fraction and Obesity), 15 mg tirzepatide reduced cardiovascular death or heart failure (HF) events to 9.9% vs. 15.3% with placebo, lowered hospitalizations, improved KCCQ-CSS (+19.5 points), increased 6MWD (+26 m), and reduced CRP (-38.8%) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, showing potent cardiometabolic effects in HFpEF patients. This evidence concerns the gene CRP and obesity due to melanocortin 4 receptor deficiency.