Benefits and risks of drug combination therapy for chronic metabolic diseases Chronic metabolic diseases are becoming increasingly prevalent and have become major public health issues worldwide. The primary metabolic diseases encompassed obesity, diabetes, non-alcoholic fatty liver disease, hyperlipidemia, and gout. Given the multifactorial nature of metabolism-related diseases, their prevention and treatment necessities multi-target strategies to tackle the physiological and metabolic impairments. The current strategies for the management of chronic metabolic diseases included lifestyle modification, balanced diet, appropriate exercise, and pharmacological interventions. However, due to the multifaceted pathophysiology underlying these metabolic disorders, developing effective therapeutic and preventive measures has so far been challenging. Current therapeutics for metabolic diseases varied in their ability to improve patient outcomes. For instance, antidiabetic drugs may elicit varying response in patients, some of which may be less favorable or even lead to adverse outcomes. To overcome these challenges, combining medications with diverse mechanism of actions held great promises to produce additive or synergistic effects aiming at reducing macrovascular and microvascular complications associated with metabolic diseases. Xie et al. reviewed that combinations therapy offers significant advantages for diabetes management. Firstly, combination therapy could regulate diabetes through multiple mechanisms and pathways, which may compensate for the limitations of monotherapy and achieve better glucose control. Secondly, combination therapy can potentially allow for the dosage reduction of individual therapies, thereby alleviating the adverse events and improving the patient tolerance. Finally, combination therapy could be tailored to specific patient conditions to provide more personalized treatment strategies. Lifestyle modification, especially dietary habits, remains the fundamental strategy for the management of metabolic-related diseases. The mendelian randomization analysis conducted by Yu et al. revealed that tea intake has no significant genetic predisposition effect on uric acid, gout, or idiopathic gout. However, they observed that tea intake does have a significant effect on the genetic predisposition of gout due to impairment of renal function. This effect may be attributed to its role in protecting renal function and regulating intestinal function. Therefore, tea intake could be encouraged as a potential dietary treatment for patients with gout associated Frontiers in Endocrinology frontiersin.org 01