Effects of tirzepatide (GIP/GLP-1 dual receptor agonist) on cardiorenal biomarkers and functional capacity in heart failure: a systematic review and meta-analysis
- Design
- Meta-analysis · 5406 participants · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: a review scoped to people with heart failure, a condition the target population does not have, and framed around heart failure with obesity; no age, BMI or diabetes data are given for the pooled participants.
- Could weight loss explain it?
- PossiblyNo weight change, HbA1c or mediation analysis is reported; the biomarker, symptom and walking-distance changes are not separated from tirzepatide's weight loss.
- Study tier
- Study tier 2MODERATE: a meta-analysis pooling 5 RCTs and 2 observational studies on mainly biomarker outcomes, with heterogeneity for NT-proBNP (I2 = 58.1%) and functional and renal results from single trials.
- Assessment
- Version 3 · Two reviewers differed; settled by a recorded ruling · Oct 19, 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.
This meta-analysis pooled seven studies (5 randomised trials and 2 observational studies; 5406 participants) of tirzepatide in heart failure. Compared with placebo or standard care, tirzepatide lowered the inflammation marker hsCRP by 34.3% and the heart-strain marker NT-proBNP by 17.6%. Gains in symptom scores, walking distance and kidney measures came from single trials only, and weight loss was not separated from these effects.
01Findings
What the study reported
- Drugs
- Tirzepatide
- Comparator
- placebo or standard of care
- Primary outcome
- cardiorenal biomarkers (NT-proBNP, hsCRP), functional capacity (KCCQ-CSS, 6-minute walk) and renal outcomes in heart failure
- Effect
- Pooled: hsCRP -34.3% (95% CI -38.4% to -30.1%; 6 studies); NT-proBNP -17.6% (95% CI -26.7% to -8.5%; 3 studies). Single trial (SUMMIT): KCCQ-CSS +5.1 points, 6 MWT +15.8 m; eGFR +2.90 mL/min/1.73 m2/year; UACR -25.0%.
- 95% confidence interval
- 95% CI: -38.4% to -30.1% (hsCRP); NT-proBNP 95% CI: -26.7% to -8.5%
- P value
- P < .0001 (hsCRP); P = .0001 (NT-proBNP)
- Follow-up
- Not stated
- Adverse events
- not reported in abstract
- Limitations
- Biomarker-led meta-analysis mixing RCTs and observational studies, with moderate heterogeneity for NT-proBNP; functional and renal results come from single trials and are hypothesis-generating.
Who was studied
- Obesity status
- not reported in abstract
- Diabetes status
- not reported in abstract
- Cvd status
- heart failure required (review scope)
- Ckd status
- not reported in abstract
- Baseline condition
- heart failure
- Sample size
- 5406
- Inclusion exclusion
- RCTs and prospective observational studies of tirzepatide vs placebo or standard of care reporting the listed biomarker, functional or renal outcomes
Study quality details
- Study design
- Meta-analysis
- Sample size
- 5406
- Randomization
- yes
- Blinding
- not stated
- Comparator
- placebo or standard of care
- Follow up duration
- not stated
- Outcome type
- mixed
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% CI: -38.4% to -30.1% (hsCRP); NT-proBNP 95% CI: -26.7% to -8.5%
- Risk of bias
- not assessed
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- not reported in abstract
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated clinical benefits in heart failure with preserved ejection fraction (HFpEF) and obesity. However, its effects on cardiorenal biomarkers and functional capacity have not been comprehensively synthesized. We hypothesized that tirzepatide produces significant reductions in cardiorenal biomarkers and improvements in functional capacity compared to placebo or standard of care. [METHODS] This systematic review and meta-analysis (PROSPERO: CRD42026137255) searched PubMed, Embase, CENTRAL, Web of Science, and Scopus from inception to April 17, 2026, without restrictions. Randomized controlled trials and prospective observational studies reporting NT-proBNP, high-sensitivity C-reactive protein (hsCRP), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), 6-minute walk test (6 MWT), or renal outcomes with tirzepatide vs placebo or standard of care were included. Data were pooled using random-effects models with Hartung-Knapp-Sidik-Jonkman adjustment. [RESULTS] Seven studies (5 RCTs, 2 observational; 5406 participants) were included. Tirzepatide significantly reduced hsCRP by 34.3% (95% CI: -38.4% to -30.1%; P < .0001; I2 = 0.0%; 6 studies) and NT-proBNP by 17.6% (95% CI: -26.7% to -8.5%; P = .0001; I2 = 58.1%; 3 studies). In the SUMMIT trial, KCCQ-CSS improved by 5.1 points (P < .001) and 6 MWT by 15.8 m (P = .004). Single-trial data demonstrated estimated glomerular filtration rate (eGFR) preservation (+2.90 mL/min/1.73 m2/year; 95% CI: 0.94 to 4.86) and urine albumin-to-creatinine ratio reduction (-25.0%; 95% CI: -36.0% to -13.0%). [CONCLUSION] Tirzepatide produces consistent anti-inflammatory effects and significant natriuretic peptide reductions, supported by moderate Grading of Recommendations Assessment, Development and Evaluation certainty. Evidence for functional and renal outcomes remains limited to single-trial analyses and should be considered hypothesis-generating pending larger dedicated heart failure trials. [PROSPERO REGISTRATION] CRD42026137255.