GLP-1 Medicines and Heart Failure: Why the Specific Trial Matters

Heart failure isn't one single condition. In heart failure with preserved ejection fraction (HFpEF), people can have breathlessness, swelling and low exercise tolerance even though the heart's pumping percentage looks normal. Obesity is closely linked with HFpEF, so researchers have tested GLP-1-based medicines in people who have both. These trials measured symptoms, physical function and, in one case, hospital-level heart-failure events, not just body weight.

Two trials that asked related but different questions

STEP-HFpEF (semaglutide). This trial randomly assigned 529 adults with HFpEF and a BMI of 30 or higher (without diabetes) to weekly semaglutide 2.4 mg or placebo for 52 weeks. Its main measures were symptoms and physical limitations, scored on the Kansas City Cardiomyopathy Questionnaire (KCCQ), plus body weight. Scores improved by about 17 points with semaglutide versus about 9 with placebo, weight fell about 13% versus about 3%, and six-minute walk distance improved by about 20 meters more than placebo. It was not designed to show whether hospitalizations or deaths were reduced. It was funded by Novo Nordisk.

SUMMIT (tirzepatide). This trial randomly assigned 731 adults with HFpEF and a BMI of 30 or higher to weekly tirzepatide (up to 15 mg) or placebo, with a median follow-up of about two years. Cardiovascular death or a worsening heart-failure event occurred in 9.9% of people on tirzepatide versus 15.3% on placebo (hazard ratio 0.62). That difference came from fewer worsening heart-failure events; cardiovascular deaths were few and not lower with tirzepatide (2.2% vs 1.4%, a difference that could be due to chance). KCCQ scores also improved more with tirzepatide. Stopping the drug because of side effects, mainly gastrointestinal, was more common with tirzepatide (6.3% vs 1.4%). It was funded by Eli Lilly.

Because these trials used different medicines, populations and endpoints, they shouldn't be ranked against each other as if they were one head-to-head study.

What's the regulatory status?

As of October 2026, heart failure is not a listed indication on the US labels for Wegovy, Ozempic, Zepbound or Mounjaro. Lilly withdrew its US application to add HFpEF to tirzepatide's label in 2025. Regulators in other countries may describe these results differently in their product information, so local labels can vary.

What the findings do not mean

They don't mean everyone with heart failure should take a GLP-1 medicine, or that one replaces standard heart-failure treatment. Both trials focused on HFpEF with obesity; people with reduced ejection fraction (HFrEF) are a different group. The type of heart failure, other conditions, other medicines and the product's current label all matter. A better symptom score is meaningful, but it isn't the same as a cure.

What about shortness of breath?

Seek urgent care for chest pain, fainting, severe breathlessness or breathlessness at rest. Contact your care team promptly about breathing that's getting worse, new swelling in your legs or belly, needing more pillows to sleep, or rapid weight gain over a few days, which can signal fluid build-up. If you already have heart failure, follow the action plan your clinician gave you. Don't assume a symptom is caused by weight or by a medication.

Questions to take to your care team

• Does the trial population resemble my type of heart failure?
• How would my existing heart-failure medicines be managed?
• Which outcomes will we monitor, and what should prompt an urgent call?

Please don't stop or change prescribed heart or blood-pressure medicines because your weight is changing; your prescriber can review that with you.

This field is moving quickly, and the evidence is encouraging for selected groups. The careful takeaway is that decisions should be tied to specific diagnoses and products, not generalized to every GLP-1 medicine or every heart condition. For the separate question of heart attack and stroke risk, see what the SELECT trial found.