SUMMIT (secondary analysis)
Trial question
What is the effect of tirzepatide on circulatory overload and end-organ damage in patients with HFpEF and obesity?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
54.0% female
46.0% male
N = 731
731 patients (393 female, 338 male).
Inclusion criteria: patients with HFpEF and obesity.
Key exclusion criteria: major cardiovascular event in the last 90 days; acute decompensated HF in the past 4 weeks; noncardiac causes of functional impairment; uncontrolled diabetes; pancreatitis; proliferative diabetic retinopathy or diabetic maculopathy.
Interventions
N=364 tirzepatide (initiated at 2.5 mg SC once weekly and increased by 2.5 mg every 4 weeks to a maintenance dose of 15 mg once weekly, and continued for a total of 52 weeks).
N=367 placebo (matching placebo once weekly for at least 52 weeks).
Primary outcome
Reduction in systolic blood pressure at week 52
4.6 mmHg
-0.1 mmHg
4.6 mmHg
3.4 mmHg
2.3 mmHg
1.1 mmHg
0.0 mmHg
-1.1 mmHg
Tirzepatide
Placebo
Significant
increase ▲
Significantly greater reduction in SBP at week 52 (4.6 mmHg vs. -0.1 mmHg; ETD 4.7, 95% CI 2.5 to 6.8).
Secondary outcomes
Significantly greater reduction in hs-CRP at week 52 (39.8% vs. 4.1%; ETD 37.2, 95% CI 27.3 to 45.7).
Significantly greater improvement in eGFR at week 52 (2.6 mL/min/1.73 m² vs. -0.3 mL/min/1.73 m²; ETD 2.9, 95% CI 0.9 to 4.9).
Significantly greater reduction in troponin-T levels at week 52 (9.6% vs. -0.9%; ETD 10.4, 95% CI 3.6 to 16.7).
Conclusion
In patients with HFpEF and obesity, tirzepatide was superior to placebo with respect to reduction in SBP at week 52.
Reference
Barry A Borlaug, Michael R Zile, Christopher M Kramer et al. Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial. Nat Med. 2025 Feb;31(2):544-551.
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