Tirzepatide data: safety always comes first!

INTRODUCTION: Tirzepatide, a dual GIP and GLP-1 receptor agonist, offers unprecedented efficacy for type 2 diabetes and obesity. Due to its rapid global adoption, understanding its complete safety spectrum is urgently needed to guide responsible prescribing and mitigate public health risks. AREAS COVERED: A literature search was conducted using PubMed and other public databases available to evaluate current evidence on the efficacy, safety, and metabolic impact of tirzepatide. The research discussed encompasses clinical trials and real-world data detailing the glycemic and weight reduction benefits of the drug. We examine its overall tolerability, covering common gastrointestinal events, including its high comparative risk for severe gastrointestinal events and treatment discontinuation, rare risks such as gallbladder and thyroid disorders, and the complex impact of the drug on skeletal muscle mass. EXPERT OPINION: While tirzepatide represents a paradigm shift in metabolic therapy, clinical management must evolve toward precision phenotyping to individualize patient risk-benefit trajectories. Future research must prioritize long-term functional outcomes to ensure that disease-modifying benefits are not offset by treatment-induced sarcopenia.