Phase 3 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

Obesity · Heart Failure With Preserved Ejection Fraction (HFpEF)

Bottom Line

View on ClinicalTrials.gov: NCT04847557 ↗

Enrolled (actual)

731

Serious AEs

26.0%

Results posted

Aug 2025

Primary outcome: Primary: 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

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Tirzepatide (Drug); Placebo (Other)
Age: Adult, Older Adult · 40+ yrs
Sex: All
Sponsor: Eli Lilly and Company
Primary completion: Jul 2024

Outcome Measures

Outcome	Result	p-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	—

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.

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). 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.