The purpose of this research study is to evaluate the safety and effectiveness of tirzepatide compared to placebo (an inactive substance) in the treatment of individuals with Heart Failure with Preserved Ejection Fraction (HFpEF) and obesity.

Participants will undergo a screening visit where they will have a physical exam to asses health and blood will be drawn. If the blood tests show that a participant qualifies to continue, then they will be randomly assigned to either tirzepatide or placebo. Each participant will have a 50:50 chance of being on tirzepatide (like the flip of a coin.) Both tirzepatide and placebo will be supplied as a single dose in an injectable pen device. Subjects will inject the study drug under the skin (or subcutaneous) once a week with the injectable pen. Participation will last at least 52 weeks and may last up to 120 weeks.

Tirzepatide has been proven to provide significant body weight loss and improvement of fat and sugar metabolism in patients with type 2 diabetes. Body weight percent reduction in this study is estimated to be 15% to 16%.