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

OBJECTIVES: To comprehensively synthesize and quantify the multiorgan 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 of tirzepatide (≥24 weeks) reporting on cardiovascular, heart failure, renal, metabolic dysfunction-associated steatohepatitis (MASH), obstructive sleep apnea, blood pressure, lipids, quality of life, body composition, or inflammatory outcomes. Data from 17 randomized controlled trials (N = 25 847) were pooled using random-effects models, with risk of bias assessed via Cochrane Risk of Bias 2 and evidence certainty rated using Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS: Tirzepatide demonstrated noninferiority to dulaglutide for major adverse cardiovascular events (HR 0.92, 95% CI 0.83-1.02). In heart failure outcomes in patients with preserved ejection fraction 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%), estimated glomerular filtration rate preservation (+1.5 mL/min/year), and high-sensitivity C-reactive protein reduction (32.9%). CONCLUSIONS: Tirzepatide provides clinically significant, multiorgan 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.