Heart failure with preserved ejection fraction (HFpEF) affects millions of people—and until recently, treatment options were limited. The heart pumps normally, but it's stiff and can't relax properly, leaving patients breathless, fatigued, and unable to exercise.
Then came STEP-HFpEF.
What Is HFpEF?
HFpEF (sometimes called "diastolic heart failure") is the most common form of heart failure in older adults, especially those with obesity. The heart muscle contracts normally, but it's stiff and doesn't fill properly between beats.
The result: fluid backup, shortness of breath, fatigue, and severely limited exercise capacity. Simple activities like climbing stairs or walking to the mailbox become exhausting.
Until recently, the only proven treatments were diuretics (to reduce fluid) and treating underlying conditions. Nothing addressed the root problem—until GLP-1s entered the picture.
STEP-HFpEF: The Trial That Changed Everything
STEP-HFpEF enrolled 529 patients with HFpEF and obesity (BMI ≥30). Half received semaglutide 2.4mg weekly, half received placebo, for 52 weeks.
The results, published in the New England Journal of Medicine, were striking:
SUMMIT: Tirzepatide Shows Similar Promise
Following STEP-HFpEF, the SUMMIT trial tested tirzepatide in HFpEF patients with obesity. The results were equally encouraging:
- 38% reduction in the composite of cardiovascular death or worsening heart failure
- Significant improvements in symptoms and exercise capacity
- Benefits seen regardless of diabetes status
Two different GLP-1/GIP medications, two successful trials. The evidence is building rapidly.
Why Does This Work?
The benefits appear to come from multiple mechanisms:
- Weight loss: Less body mass means less work for the heart
- Reduced epicardial fat: Fat around the heart contributes to stiffness; GLP-1s reduce it
- Anti-inflammatory effects: The dramatic CRP reduction suggests benefits beyond weight
- Improved metabolism: Better glucose and lipid handling reduces cardiac stress
- Diuretic effect: GLP-1s promote sodium excretion, reducing fluid overload
What This Means for Patients
If you have heart failure with preserved ejection fraction, especially if you also have obesity, GLP-1 medications represent a genuine breakthrough. They address multiple aspects of the disease simultaneously.
Current status: The FDA approved Wegovy (semaglutide 2.4mg) for reducing cardiovascular events, though specific HFpEF approval is still being pursued. Many cardiologists are already prescribing GLP-1s for appropriate HFpEF patients based on the trial data.
- Kosiborod MN, et al. NEJM. "Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity." 2023.
- SUMMIT Trial. American Heart Association Scientific Sessions 2024.
- FDA Wegovy Cardiovascular Indication Approval. 2024.