STEP-HFpEF: semaglutide in heart failure with preserved EF

Based on STEP-HFpEF data, semaglutide is a reasonable consideration for your mother's situation. The trial enrolled a very similar patient profile — HFpEF with obesity, on background guideline-directed therapy. The FDA has not yet approved semaglutide specifically for HFpEF, but the obesity indication (Wegovy) provides an approved pathway, and many cardiologists are now using it for the obese HFpEF phenotype.

Practical considerations:

• Start at the low dose (0.25 mg) and titrate slowly — HFpEF patients tend to be older and may be more GI-sensitive
• Monitor fluid status — semaglutide has a natriuretic effect that may necessitate diuretic adjustment
• Monitor renal function — especially if she's on sacubitril-valsartan and empagliflozin (both can affect GFR)
• Ensure adequate protein intake and encourage resistance exercise to mitigate lean mass loss

The conversation with her cardiologist should reference STEP-HFpEF directly. Most cardiologists who follow the literature are aware of these data and many are already incorporating GLP-1 RAs into their HFpEF treatment algorithm.

One caveat to add: there's an emerging HFpEF phenotype discussion that's relevant. Not all HFpEF is the same. The "obese-inflammatory" phenotype (high BMI, elevated hsCRP, metabolic syndrome) is the one where semaglutide has the strongest rationale. Other HFpEF phenotypes — elderly-fibrotic, hypertensive-hypertrophic, or cardiac amyloidosis — may not benefit as much from weight loss and anti-inflammatory effects.

STEP-HFpEF was enriched for the obese phenotype by design (BMI >= 30 required). Extrapolating to lean HFpEF patients would be inappropriate. The field is moving toward phenotype-guided HFpEF treatment, and semaglutide is the first therapy that's truly phenotype-specific in HFpEF. That's a conceptual advance even beyond the specific trial results.

Important thread. The STEP-HFpEF results represent a convergence of the obesity and heart failure fields that's long overdue. For decades, we treated obesity and HFpEF as separate problems. Now we understand that in many patients, obesity is the cause of HFpEF, and treating the obesity treats the heart failure.

Upcoming data to watch: Novo Nordisk has a larger HF outcome trial (SELECT-HF) that should provide hard endpoint data. Until then, STEP-HFpEF provides the best available evidence supporting semaglutide for the obese HFpEF phenotype.