Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity
- Design
- Randomized trial · 731 participants · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationObese HFpEF population; composite benefit driven by heart-failure events, with numerically more CV deaths on tirzepatide (few events).
- Could weight loss explain it?
- LikelyTirzepatide produces very large weight loss; mediation not analysed in abstract.
- Study tier
- Study tier 2Moderate-sized RCT with a composite driven by HF events; CV death component uninformative.
- Assessment
- Version 2 · curated · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
In 731 people with HFpEF and obesity, tirzepatide lowered the combined risk of cardiovascular death or worsening heart failure (about 10% vs 15%) over roughly two years, mainly by reducing heart-failure events. Cardiovascular deaths were slightly more frequent on tirzepatide, though numbers were tiny. Not applicable outside obesity.
01Findings
What the study reported
- Drugs
- Tirzepatide
- Dose
- up to 15 mg once weekly
- Route
- subcutaneous
- Treatment duration
- median follow-up 104 weeks
- Comparator
- placebo
- Primary outcome
- CV death or worsening heart-failure event; change in KCCQ-CSS at 52 weeks
- Effect
- HR 0.62 (9.9% vs 15.3%); worsening HF HR 0.54; CV death HR 1.58 (8 vs 5 events); KCCQ +6.9
- 95% confidence interval
- 0.41 to 0.95 (composite)
- P value
- 0.026
- Follow-up
- median 104 weeks
- Adverse events
- Discontinuation for adverse events (mainly GI) 6.3% vs 1.4%.
- Limitations
- Obese HFpEF only; modest event count.
Who was studied
- Bmi min
- 30
- Obesity status
- obesity required (BMI >= 30)
- Diabetes status
- mixed (not excluded)
- Cvd status
- HFpEF required
- Baseline condition
- heart failure with preserved ejection fraction
- Sample size
- 364
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 364
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- 52 weeks
- Outcome type
- mixed
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- 92 composite events; CV-death estimate very imprecise
- Risk of bias
- not assessed (auto)
- Funding conflicts
- yes
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Eli Lilly
- Industry funded
- Yes
- Manufacturer
- Eli Lilly
- Sponsor role
- Sponsor designed and analysed.
- Author conflicts
- Authors report Eli Lilly relationships; sponsor co-authors.
- Independent replication
- no
- Notes
- Authors declare relationships with the drug's manufacturer: Eli Lilly
Funding is shown on every study and never used to score it.
03Claims
Claims this study bears on
- Incretin therapies improve outcomes in heart failure with preserved ejection fraction and obesity.Supports
SUMMIT: HR 0.62 for CV death or worsening HF; driven by HF events (CV death HR 1.58, few events).
04Source
The source, as retrieved
Abstract
[BACKGROUND] Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes. [METHODS] 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. 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). [RESULTS] 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). 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). 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). 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. [CONCLUSIONS] Treatment with tirzepatide led to a lower risk of a composite of death from cardiovascular causes or worsening heart failure than placebo and improved health status in patients with heart failure with preserved ejection fraction and obesity. (Funded by Eli Lilly; SUMMIT ClinicalTrials.gov number, NCT04847557.).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 39555826 first ingestion |