Effects of tirzepatide (GIP/GLP-1 dual receptor agonist) on cardiorenal biomarkers and functional capacity in heart failure: a systematic review and meta-analysis
In brief
Tirzepatide lowers an inflammation marker by 34% in heart failure studies
Across seven studies involving 5,406 people, tirzepatide lowered high-sensitivity C-reactive protein by 34% and NT-proBNP by 18%. One trial also found modest improvements in symptom scores and walking distance, while kidney benefits came from single-trial data; larger heart failure studies are needed to confirm effects on function and kidney outcomes.
- Journal
- The Journal of clinical endocrinology and metabolism (Q1)
- Published
- 13 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Naseem Eisa, Mira Khoury
- PMID
- 42867450
- DOI
- 10.1210/clinem/dgag284
Why clinicians should know about it
- Picked for Biochemistry (medical) (paper of the day, 14 October 2026): Systematic review of tirzepatide metabolic biomarkers
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.