Metabolically healthy obesity or metabolically healthy overweight (MHO) is best described as being absent of any major metabolic disorder or cardiovascular diseases such as type 2 diabetes mellitus, dyslipidemia, hypertension, and atherosclerotic cardiovascular disease despite being obese or overweight. Nevertheless, MHO is being recognized as an important risk factor for the development of cardiovascular, cerebrovascular, and peripheral artery disease. In addition, these patients are at a high risk of conversion to the metabolically unhealthy phenotype. Tirzepatide is a newly developed glucose-lowering agent which acts on the glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. It has been shown to result in several highly beneficial outcomes including weight loss and a significant improvement in important metabolic parameters such as HbA1c, fasting serum glucose, and triglyceride/lipoprotein levels. These findings suggest that tirzepatide could potentially be beneficial to metabolically healthy obese or metabolically healthy overweight patients in reducing their risk of adverse cardiovascular outcomes and conversion to the metabolically unhealthy phenotype. In this review, we aim to discuss the potential benefits of using the novel anti-diabetic tirzepatide in the management of MHO to prevent the development of cardiovascular events and to decrease the likelihood of conversion to the unhealthy phenotype. We initially describe the clinical outcomes of MHO as well as the association of MHO with developing future cardiovascular events. We then delineate the currently available evidence behind the clinical effects of tirzepatide. We finally discuss the potential advantages of using tirzepatide in the management of MHO.
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