Trial results for the SUMMIT study (NCT04847557) investigating Tirzepatide in participants with heart failure with preserved ejection fraction (HFpEF) and obesity were posted on ClinicalTrials.gov on 2025-08-20. The study demonstrated that Tirzepatide significantly improved the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) by 19.51 points and reduced the first occurrence of composite heart failure outcomes by 38% compared to placebo.
Background
The SUMMIT trial, also known as "A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity," aimed to assess the efficacy and safety of Tirzepatide in this patient population.
Trial design
The SUMMIT study (NCT04847557) was a Phase 3, randomized, placebo-controlled trial that enrolled 731 participants. The study investigated Tirzepatide in individuals diagnosed with Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity. Participants were randomized to receive either Tirzepatide at its maximum tolerated dose (MTD) or a placebo.
Key results
The trial results demonstrated significant improvements across several key endpoints for Tirzepatide compared to placebo.
- For "Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)":
- Participants receiving Tirzepatide showed a least squares mean change of 19.51 (Standard Error: 1.24).
- Participants receiving placebo showed a least squares mean change of 12.68 (Standard Error: 1.25).
- A Stratified Wilcoxon analysis indicated a median difference (net) of 6.9 (95.0% CI: 3.3 to 10.6) with a p-value of 0.001.
- For "First Occurrence of the Composite Endpoint of Heart Failure (HF) Outcomes":
- There were 36 events in the Tirzepatide group compared to 56 events in the placebo group.
- A Cox Regression analysis yielded a Hazard Ratio (HR) of 0.62 (95.0% CI: 0.41 to 0.95) with a p-value of 0.026, indicating a 38% reduction in risk for Tirzepatide.
- For "Change From Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD)":
- The Tirzepatide group showed a least squares mean change of 26.04 meters (Standard Error: 3.81).
- The placebo group showed a least squares mean change of 10.10 meters (Standard Error: 3.94).
- A Stratified Wilcoxon analysis indicated a median difference (net) of 18.3 (95.0% CI: 9.9 to 26.7) with a p-value of 0.001.
- For "Percent Change From Baseline in Body Weight":
- The Tirzepatide group achieved a least squares mean reduction of -13.85% (Standard Error: 0.43).
- The placebo group achieved a least squares mean reduction of -2.24% (Standard Error: 0.46).
- An ANCOVA analysis showed an LS Mean Difference of -11.62 (95.0% CI: -12.85 to -10.38) with a p-value of 0.001.
- For "Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)":
- The Tirzepatide group showed a least squares mean reduction of -38.76% (Standard Error: 4.47).
- The placebo group showed a least squares mean reduction of -5.88% (Standard Error: 5.25).
- An ANCOVA analysis showed an LS Mean Difference of -34.91 (95.0% CI: -45.6 to -22.17) with a p-value of 0.001.
- For "Win Percentage of the Hierarchical Composite Endpoint":
- The Tirzepatide group had a win percentage of 57.90%.
- The placebo group had a win percentage of 35.43%.
- The Win Ratio was 1.63 (95.0% CI: 1.17 to 2.28).
What this means
The results from the SUMMIT trial indicate that Tirzepatide significantly improved quality of life, exercise capacity, and reduced heart failure events in individuals with HFpEF and obesity. The substantial reductions in body weight and inflammatory markers like hsCRP further support its potential benefits in this patient population. These findings suggest that Tirzepatide could be a valuable therapeutic option for managing both obesity and the symptoms associated with HFpEF.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04847557, titled "A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial," were posted on 2025-08-20 on clinicaltrials.gov.