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Zepbound for heart failure (HFpEF): the SUMMIT trial and the label

Updated Sep 30, 2026. Numbers in brackets link to the source each fact comes from.

Zepbound is not FDA-approved to treat heart failure. Its label lists two uses: weight reduction in adults with obesity or overweight plus a weight-related condition, and moderate to severe obstructive sleep apnea in adults with obesity [7] [8]. The heart failure evidence comes from one trial, SUMMIT, in people with a specific type of heart failure who also had obesity.

What SUMMIT tested

HFpEF is heart failure with preserved ejection fraction: the heart muscle is stiff and does not fill with blood easily, even though its pumping power is normal [14]. SUMMIT enrolled 731 people with heart failure, an ejection fraction of at least 50% and a BMI of at least 30 [1]. They took weekly tirzepatide, up to 15 mg, or a placebo for at least 52 weeks [1].

The trial had two main measures: a combined count of cardiovascular death or a worsening heart failure event, and the change in a 0 to 100 symptom and quality-of-life score called KCCQ-CSS [2].

What it found

The results below come from the published abstract. The median follow-up was 104 weeks [3].

Measure Tirzepatide Placebo
Cardiovascular death or worsening heart failure 9.9% [3] 15.3% [3]
Worsening heart failure events alone 8.0% [4] 14.2% [4]
Cardiovascular death alone 2.2% [4] 1.4% [4]
KCCQ-CSS change at 52 weeks (higher is better) +19.5 points [5] +12.7 points [5]
Stopped the drug because of side effects 6.3% [6] 1.4% [6]

The combined outcome happened less often on tirzepatide, with a hazard ratio of 0.62 [3]. Worsening heart failure events on their own were also less frequent, with a hazard ratio of 0.54 [4]. Cardiovascular deaths were few in both groups, and the confidence interval for that comparison ran from 0.52 to 4.83, so the trial cannot say whether tirzepatide changes the risk of dying from heart disease [4]. The side effects that led people to stop were mainly gastrointestinal [6].

What SUMMIT does not tell you

  • Other kinds of heart failure. Everyone enrolled had an ejection fraction of at least 50% [1]. Heart failure with a reduced ejection fraction was not studied.
  • People without obesity. A BMI of at least 30 was required to join [1].
  • Semaglutide. The Wegovy label, reporting its own heart-outcomes trial, says the effect on heart failure has not been established [9]. Results for tirzepatide do not transfer to other GLP-1 medicines.

Why the label has no heart failure use

The current Zepbound label names weight reduction and sleep apnea only, and it does not mention heart failure anywhere [7] [8]. Prescribing Zepbound for HFpEF itself would therefore be off-label.

What this means for coverage

Because heart failure is not a labeled use, the coverage routes CMS describes for someone with HFpEF run through weight or sleep apnea:

  • Medicare GLP-1 Bridge. CMS built the Bridge for people who take a GLP-1 to lose weight or keep it off [12]. One way to qualify is a BMI of 30 or more at the start of treatment plus a diagnosis of heart failure with preserved ejection fraction [10]. Zepbound qualifies only in its KwikPen form [11]. Details are in our Medicare GLP-1 Bridge guide and the Bridge eligibility checker.
  • Medicare Part D for sleep apnea. CMS says the moderate to severe sleep apnea use is eligible for Part D coverage [13]. That route depends on having that diagnosis, not on the heart failure.

If you have HFpEF, the decision to add tirzepatide belongs with your cardiologist and the clinician who would prescribe it, since heart failure medicines and fluid balance are managed together.

Sources

  1. In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  2. The two primary end points were a composite of adjudicated death from cardiovascular causes or a worsening heart-failure event (assessed in a time-to-first-event analysis) and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better quality of life). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  3. A total of 364 patients were assigned to the tirzepatide group and 367 to the placebo group; the median duration of follow-up was 104 weeks. Adjudicated death from cardiovascular causes or a worsening heart-failure event occurred in 36 patients (9.9%) in the tirzepatide group and in 56 patients (15.3%) in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.41 to 0.95; P = 0.026). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  4. Worsening heart-failure events occurred in 29 patients (8.0%) in the tirzepatide group and in 52 patients (14.2%) in the placebo group (hazard ratio, 0.54; 95% CI, 0.34 to 0.85), and adjudicated death from cardiovascular causes occurred in 8 patients (2.2%) and 5 patients (1.4%), respectively (hazard ratio, 1.58; 95% CI, 0.52 to 4.83). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  5. At 52 weeks, the mean (±SD) change in the KCCQ-CSS was 19.5±1.2 in the tirzepatide group as compared with 12.7±1.3 in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  6. Adverse events (mainly gastrointestinal) leading to discontinuation of the trial drug occurred in 23 patients (6.3%) in the tirzepatide group and in 5 patients (1.4%) in the placebo group. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  7. to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition. dailymed.nlm.nih.gov, read Sep 27, 2026.
  8. to treat moderate to severe obstructive sleep apnea (OSA) in adults with obesity. dailymed.nlm.nih.gov, read Sep 27, 2026.
  9. Effect on heart failure has not been established. dailymed.nlm.nih.gov, read Sep 27, 2026.
  10. has a BMI greater than or equal to thirty (≥30) at the time of initiating GLP-1 therapy with a diagnosis of one or more of the following: (A) heart failure with preserved ejection fraction cms.gov, read Sep 27, 2026.
  11. an eligible GLP-1 drug is any of the following products when used to reduce excess body weight and maintain weight reduction: Foundayo®, Wegovy® (injection and tablets), and Zepbound® (KwikPen®). cms.gov, read Sep 27, 2026.
  12. The Medicare GLP-1 Bridge was designed to increase access to GLP-1s for beneficiaries who seek the drug solely to reduce excess body weight or maintain weight reduction. cms.gov, read Sep 27, 2026.
  13. Type 2 diabetes, moderate to severe obstructive sleep apnea, and noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) indications are eligible for Part D coverage. cms.gov, read Sep 27, 2026.
  14. Your heart muscle is stiff and does not fill up with blood easily even though pumping power is normal. This is called diastolic heart failure, or heart failure with a preserved ejection fraction (HFpEF). medlineplus.gov, read Sep 27, 2026.

This page reports what official sources say; it is not medical advice. Medical disclaimer.