Semaglutide in HFpEF: STEP-HFpEF Trial Results Explained

Last reviewed 2026-10-04 by Jack Mayeux, APRN, FNP. This page is clinical content and is reviewed on a regular schedule.

Medically reviewed by Jack Mayeux, FNP

In obesity-related heart failure, semaglutide improved symptoms, walking distance and cut inflammation (CRP) by ~44%.

This article walks through the N Engl J Med (2023) (https://doi.org/10.1056/NEJMoa2306963) paper in plain English: what was studied, what changed, what the limits are, and what it does not prove. Full citation and DOI link (https://doi.org/10.1056/NEJMoa2306963) are at the end, with a PubMed record (https://pubmed.ncbi.nlm.nih.gov/37622681/).

What the study found

STEP-HFpEF randomized 529 adults with heart failure with preserved ejection fraction and a BMI of 30 or higher to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Endpoints included symptom scores, body weight, walking distance and CRP.

Semaglutide improved the symptom score by 16.6 points vs 8.7, walking distance by 21.5 m vs 1.2 m, and lowered CRP by 43.5% vs 7.3%, with fewer serious adverse events. Outcomes were symptoms and function over a year, and the trial used brand-name semaglutide; compounded versions are not FDA-approved and were not studied.

Key finding (from the study record): KCCQ symptom score +16.6 vs +8.7; 6-min walk +21.5 m vs +1.2 m; CRP -43.5% vs -7.3%; serious AEs 13.3% vs 26.7%.

How the study was done

• Design: Double-blind RCT (STEP-HFpEF) • Who was studied: 529 patients with HFpEF and BMI >=30 • Journal / year: N Engl J Med (2023) • First author: Kosiborod MN et al.

From the abstract: BACKGROUND: Heart failure with preserved ejection fraction is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in persons with obesity. No therapies have been approved to target obesity-related heart failure with preserved ejection fraction. METHODS: We randomly assigned 529 patients who had heart failure with preserved ejection fraction and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks.

What it means — and what it does not

Useful takeaway: In obesity-related heart failure, semaglutide improved symptoms, walking distance and cut inflammation (CRP) by ~44%.

Limits and caveats: 52 weeks; symptom endpoints, not hard outcomes. Brand-name drug.

This evidence can inform a conversation with a licensed provider. It is not a guarantee of similar results for you, and it is not a recommendation to start, stop, or change any medication on your own.

Compounded-drug note: The trial used a branded product. Compounded versions of GLP-1 medications are not FDA-approved and are not the branded drugs used in these trials.

Related research we cite

• Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (https://doi.org/10.1056/NEJMoa2307563) — N Engl J Med (2023); also on PubMed (https://pubmed.ncbi.nlm.nih.gov/37952131/). Takeaway: In people with heart disease and excess weight but no diabetes, weekly semaglutide cut heart attacks, strokes and CV deaths by 20%.

How this connects to care

A2Z serves men in Utah with telehealth evaluation, labs, and provider-guided plans when appropriate. The TRT program is $149/month and includes initial labs only. Tadalafil and enclomiphene, sermorelin, and tirzepatide (compounded, not FDA-approved) are separate products.

Relevant pages on this site:

• Tirzepatide (https://a2ztrt.com/tirzepatide) (branded trial drugs are not the same as compounded products, which are not FDA-approved) • Tirzepatide vs. semaglutide (https://a2ztrt.com/tirzepatide-vs-semaglutide) (branded trial drugs are not the same as compounded products, which are not FDA-approved) • TRT program (https://a2ztrt.com/trt)

FAQ

What did this study actually find?

In obesity-related heart failure, semaglutide improved symptoms, walking distance and cut inflammation (CRP) by ~44%. The design was: Double-blind RCT (STEP-HFpEF). Population: 529 patients with HFpEF and BMI >=30.

Does this mean I should start treatment?

No. Research informs care; it does not prescribe it. A licensed provider reviews your symptoms, labs, and history before any decision. Results vary.

What are the main limits of this evidence?

52 weeks; symptom endpoints, not hard outcomes. Brand-name drug.

Was this the compounded drug some clinics sell?

No. The trial used a branded, FDA-approved product. Compounded copies are not FDA-approved and are not the drug studied.

Did testosterone protect the heart?

TRAVERSE was built to test safety (noninferiority), not heart protection. Meeting noninferiority is not the same as proving benefit.

Keep reading

• Sleep Extension Cut Daily Calories by 270 in Adults With Overweight (https://a2ztrt.com/post/sleep-extension-calories) • Can You Drink Alcohol on TRT? What Men Should Know (https://a2ztrt.com/post/can-you-drink-alcohol-on-trt) • Does TRT Cause Hair Loss? What the Evidence Actually Says (https://a2ztrt.com/post/does-trt-cause-hair-loss) • What Is a Normal Testosterone Level, Really? (https://a2ztrt.com/post/what-is-a-normal-testosterone-level)

Reference

Kosiborod MN et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023. https://doi.org/10.1056/NEJMoa2306963 (https://doi.org/10.1056/NEJMoa2306963) · PubMed 37622681 (https://pubmed.ncbi.nlm.nih.gov/37622681/).

Next step

Start a free consult in Utah (https://a2ztrt.com/contact). Bring your questions — including anything this study raised for you.

The TRT program is $149/month and includes initial labs only. Tadalafil and enclomiphene, sermorelin, and tirzepatide (compounded, not FDA-approved) are separate products.

Talk to a licensed provider. Results vary. Not medical advice.