Effects of Tirzepatide in Obesity-Related HFpEF by Sex: A Prespecified Secondary Analysis From the SUMMIT Trial
- Design
- Randomized trial · 364 participants · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Participants had obesity/overweight (BMI ≥30 required).
- Could weight loss explain it?
- Possibly[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 2[Auto] Randomized trial of moderate size; outcome type and follow-up limit certainty (auto-provisional).
- Assessment
- Version 1 · automatic, not yet reviewed by a person · 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.
[Auto, unreviewed; quoted from abstract conclusions] Compared with men, women with obesity-related HFpEF have greater adiposity, symptom severity, and poorer exercise capacity but lower left ventricular mass and paracardiac fat deposition. Despite these differences, tirzepatide resulted in consistent benefits across multiple domains of HF severity that did not differ by sex. (A Study of Tirzepatide
01Findings
What the study reported
- Drugs
- Tirzepatide
- Comparator
- placebo
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- 52 weeks
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Bmi min
- 30
- Obesity status
- obesity/overweight present (all or most)
- Cvd status
- cardiovascular disease present in population (see abstract)
- 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
- not stated
- 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
- not extracted
- Risk of bias
- not assessed (auto)
- Funding conflicts
- no
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- NHLBI NIH HHS
- Industry funded
- No
- Manufacturer
- Novo Nordisk, Eli Lilly, Lilly, AstraZeneca, Boehringer Ingelheim, Amgen, Roche, Innovent
- Sponsor role
- no manufacturer funding identified
- Author conflicts
- Funding Support and Author Disclosures The SUMMIT trial was funded by Eli Lilly and Company. Dr Borlaug has received grants R01 HL128526, R01 HL162828, and U01 HL160226 from the National Heart, Lung, and Blood Institute; grant W81XWH2210245 from the United States Department of Defense; and has received grants from the Schoen Foundation AstraZeneca, Axon, Corvia, Novo Nordisk, and Tenax Therapeutics; he has received consulting fees from Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations; and is named inventor (US Patent number 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. Dr Zile has received research support from the Department of Veterans Affairs; and consulting fees from Abbott, Adona Medical, Aria CV, Avery Therapeutics Inc, Boehringer Ingelheim, Boston Scientific, Cardiovascular Research Foundation (CRF) Clinical Trials Center, CVRx, DIASTOL Therapeutics, LLC, EBR, Edwards, Lilly, GenKardia, Innoventric, KestraMedical, Medtronic, Merck, Morphic Therapeutics, Novartis, Pulnova, Salubris Biotherapeutics, Sonata, SRNALYTICS Inc, V-WAVE, and Vectorious. Dr Kramer has received consulting fees from Eli Lilly. Dr Litwin has been on the patient selection committee for Corvia and Axon; and has received consulting fees from Novo Nordisk and Lilly. Drs Hurt, Murakami, and Ou are employed
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Eli Lilly
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] The SUMMIT trial showed that the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide decreased risk of cardiovascular death or worsening heart failure (HF) in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Women outnumber men with HFpEF, and there are sexual dimorphisms in the relationships between body fat and pathophysiology that could influence response to tirzepatide. [OBJECTIVES] This study aims to compare baseline characteristics and effects of tirzepatide on primary and other endpoints in women and men with obesity-related HFpEF. [METHODS] In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m2 were randomly assigned to tirzepatide (n = 364) or placebo (n = 367). The primary outcomes were time to cardiovascular death or worsening HF and change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) at 52 weeks. Key secondary outcomes included changes in 6-minute walk distance (6MWD), C-reactive protein, and body weight at 52 weeks. Baseline characteristics and effects of tirzepatide on primary and secondary endpoints were contrasted by sex. [RESULTS] Compared with men (n = 338, 46.2%), women with obesity-related HFpEF (n = 393, 53.8%) had greater BMI, waist to height ratio (WHtR), symptom severity (higher NYHA functional class, lower KCCQ-CSS), and poorer exercise capacity (lower 6MWD), whereas men had greater left ventricular remodeling and paracardiac fat. Greater baseline BMI or WHtR were correlated with lower KCCQ-CSS and 6MWD in women and men, with no interaction, but higher WHtR was associated with poorer kidney function exclusively in women (interaction P = 0.043). The effect of tirzepatide on the risk of worsening HF or cardiovascular death did not differ in women and men (HR: 0.66 and 0.61, respectively, interaction P = 0.81), with no heterogeneity of effect on KCCQ-CSS at 52 weeks (8.1- and 5.5-point placebo-corrected improvement, respectively, interaction P = 0.43) or 6MWD (18 m and 15 m placebo-corrected improvement, respectively, interaction P = 0.76). Among patients randomized to tirzepatide, decreases in body weight on treatment were more strongly associated with improvements in KCCQ-CSS in women than men (interaction P = 0.0058). [CONCLUSIONS] Compared with men, women with obesity-related HFpEF have greater adiposity, symptom severity, and poorer exercise capacity but lower left ventricular mass and paracardiac fat deposition. Despite these differences, tirzepatide resulted in consistent benefits across multiple domains of HF severity that did not differ by sex. (A Study of Tirzepatide [LY3291876] in Participation With Heart Failure With Preserved Ejection Fraction [HFpEF] and Obesity [SUMMIT]; NCT04847557).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 42417681 first ingestion |