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Phase 3 Completed N=731 Randomized Double-blind Treatment

A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial

Source: ClinicalTrials.gov NCT04847557 ↗
Enrolled (actual)
731
Serious AEs
26.0%
Results posted
Aug 2025
Primary outcomePrimary: Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) — 19.51; 12.68 Score on a scale — p=<0.001
◆ Published Evidence
Highly cited
145citations · ~145 / year
Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy.
Journal of the American College of Cardiology · 2025 · Open access · Likely link

Summary

The main purpose of this study is to assess the efficacy and safety of Tirzepatide (LY3298176) in participants with heart failure with preserved ejection fraction and obesity.

Linked Publications (5)

  • Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy.
    Journal of the American College of Cardiology · 2025 · 145 citations · Open access · Likely link
  • Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity.
    Circulation · 2025 · 60 citations · Open access · Likely link
  • Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial.
    Journal of the American College of Cardiology · 2025 · 37 citations · Likely link
  • Impact of Body Mass Index, Central Adiposity, and Weight Loss on the Benefits of Tirzepatide in HFpEF: The SUMMIT Trial.
    Journal of the American College of Cardiology · 2025 · 31 citations · Likely link
  • Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity: A Prespecified Stratification-Based Analysis.
    Journal of the American College of Cardiology · 2025 · 17 citations · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)
19.51; 12.68 <0.001 sig
PRIMARY
First Occurrence of the Composite Endpoint of Heart Failure (HF) Outcomes
36; 56 0.026 sig
SECONDARY
Change From Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD)
26.04; 10.10 <0.001 sig
SECONDARY
Percent Change From Baseline in Body Weight
-13.85; -2.24 <0.001 sig
SECONDARY
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
-38.76; -5.88 <0.001 sig
SECONDARY
Win Percentage of the Hierarchical Composite Endpoint
57.90; 35.43
SECONDARY
Percentage of Participants With New York Heart Association (NYHA) Class Change
33.27; 20.39
SECONDARY
Number of Participants With Time to All-Cause Death
19; 15
SECONDARY
Number of Participants With Time to First Occurrence of HF Events
29; 52
SECONDARY
Number of HF Events and All-Cause Death
61; 82
SECONDARY
Number of Recurrent HF Events
44; 68

Eligibility Criteria

Inclusion Criteria

  • Have a diagnosis of stable heart failure (NYHA class II-IV) and left ventricular ejection fraction (LVEF) ≥50%
  • Elevated NT-proBNP (N-terminal pro B-type natriuretic peptide) > 200 picogram/milliliter (pg/ml) for participants without atrial fibrillation (AF), or >600 pg/ml for participants with AF, Structural heart disease (Left atrial enlargement) or Elevated left ventricular filling pressure
  • Estimated glomerular filtration rate (eGFR) <70 milliliter (ml)/minute (min)/1.73m² at screening, or HF decompensation within 12 months of screening,
  • Stable dose of heart failure medications within 4 weeks of screening
  • Body mass index (BMI) ≥30 kilograms per meter squared (kg/m²)
  • 6MWD 100-425 meters
  • KCCQ CSS ≤80

Exclusion Criteria

  • Have had a major cardiovascular event within the last 90 days of screening
  • Have had acute decompensated heart failure within 4 weeks of screening
  • Have non cardiac causes of functional impairment such as pulmonary arterial hypertension (PAH), severe chronic obstructive pulmonary disease (COPD), anemia, thyroid disease, musculoskeletal disease or orthopedic conditions
  • Presence of cardiac amyloidosis, cardiac accumulation disease, cardiomyopathy and severe valvular heart disease
  • HbA1c ≥9.5% or uncontrolled diabetes
  • History of proliferative diabetic retinopathy or diabetic maculopathy
  • Have a history of pancreatitis
  • eGFR <15 mL/min/1.73 m² or requiring dialysis at screening
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04847557) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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