Tirzepatide Beyond Diabetes and Obesity: Systematic Review and Meta-Analysis of Multisystem Therapeutic Benefits

Apr 30, 2026Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

Tirzepatide's potential health benefits beyond diabetes and obesity: A review and analysis

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Abstract

Tirzepatide led to 38% reduction in cardiovascular death or heart failure events in patients with heart failure with preserved ejection fraction (HFpEF).

Tirzepatide showed non-inferiority to dulaglutide for major adverse cardiovascular events, with a hazard ratio of 0.92.
In a pooled analysis of 17 randomized controlled trials with 25,847 participants, tirzepatide resulted in MASH resolution in 62% of patients.
There was a clinically significant reduction in the apnea-hypopnea index by 21.9 events per hour.
Systolic blood pressure decreased by an average of 5.8 mmHg, and triglyceride levels were reduced by 19.6%.
Tirzepatide contributed to an increase in estimated glomerular filtration rate (eGFR) of +1.5 mL/min/year and a reduction in high-sensitivity C-reactive protein (hsCRP) by 32.9%.

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OBJECTIVES: To comprehensively synthesize and quantify the multi-organ effects of tirzepatide across 10 health domains beyond its primary indications for type 2 diabetes and obesity.

METHODS: We searched PubMed, Embase, and CENTRAL through January 2026 for randomized controlled trials (RCTs) of tirzepatide (≥24 weeks) reporting on cardiovascular, heart failure, renal, MASH, obstructive sleep apnea, blood pressure, lipids, quality of life, body composition, or inflammatory outcomes. Data from 17 RCTs (N=25,847) were pooled using random-effects models, with risk of bias assessed via Cochrane RoB 2 and evidence certainty rated using GRADE.

RESULTS: Tirzepatide demonstrated non-inferiority to dulaglutide for major adverse cardiovascular events (HR 0.92, 95% CI 0.83-1.02). In HFpEF patients, it reduced cardiovascular death or heart failure events by 38% (HR 0.62, 95% CI 0.41-0.95). Additional benefits included: MASH resolution in 62% of patients (RR 5.33), clinically significant apnea-hypopnea index reduction (21.9 events/hour), systolic blood pressure reduction (5.8 mmHg), triglyceride reduction (19.6%), eGFR preservation (+1.5 mL/min/year), and hsCRP reduction (32.9%).

CONCLUSIONS: Tirzepatide provides clinically significant, multi-organ benefits across heart failure, MASH, sleep apnea, blood pressure, lipids, and inflammation. Supported by moderate-to-high certainty evidence, it emerges as a comprehensive cardiometabolic protective agent. However, findings for domains like heart failure and MASH resolution rely on few trials, necessitating cautious interpretation regarding generalizability.

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Tirzepatide Beyond Diabetes and Obesity: Systematic Review and Meta-Analysis of Multisystem Therapeutic Benefits

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