Tirzepatide in Metabolic Diseases: Clinical Efficacy and Safety Beyond Diabetes and Obesity

Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has attracted substantial attention for its exceptional efficacy in managing type 2 diabetes and obesity. Emerging evidence suggests that tirzepatide may also exert broad therapeutic benefits in cardiovascular diseases, metabolic dysfunction-associated steatotic liver disease, and chronic kidney disease. However, its potential clinical risks are increasingly being recognized. This review begins by outlining the structural and pharmacological advantages of tirzepatide. We then comprehensively evaluate recent clinical evidence, including randomized controlled trials and real-world studies, based on a comprehensive literature search, to analyze its efficacy and safety for metabolic disorders. Tirzepatide exhibits considerable promise in treating multiple metabolic diseases; however, its therapeutic benefits must be carefully weighed against potential risks. Conclusions on cardiorenal benefits are supported by high-level outcome trials, while the evidence for hepatic, renal and musculoskeletal effects is exploratory or preliminary. Further large-scale, long-term studies remain essential to fully elucidate its mechanisms of action and overall clinical impact, given the current safety signals and other evidence are largely based on case reports, post hoc analyses, and non-prespecified endpoints. Continued pharmacovigilance is also crucial to identify and mitigate potential adverse drug reactions in diverse patient populations, especially for rare but serious events identified through spontaneous reporting systems.