Updates In Common Genetic Variants May Help Guide Drug Selection For Treating Uncontrolled Diabetes

Type 2 diabetes mellitus (T2DM) is a common, lifelong metabolic disorder. Adults with T2DM bear a greater burden of cardiometabolic risk factors than the general popula-tion. T2DM presents as a spectrum of clinical manifestations, where uncontrolled dia-betes leads to progressive or irreparable damage to various organs. Neurologic end-organ damage due to uncontrolled diabetes may include neuropathy, nephropa-thy, and retinopathy. T2DM can be categorized into three levels: (1) prediabetes, with a blood sugar level between 110 and 125 mg/dL, (2) T2DM, with a blood sugar level higher than 126 mg/dL, and (3) uncontrolled T2DM, with a blood sugar level exceeding 180 mg/dL despite multiple medications. If blood sugar remains consistently high in level 1, it may cause pathological and functional changes in healthy vascular tissues and various systems, often without noticeable clinical symptoms. However, the latter two levels are important for identifying individuals at high risk of nerve damage, kid-ney damage, and cardiovascular (CV) events. Research shows that reducing modifia-ble risk factors can help prevent the progression from prediabetes to T2DM, while an-tidiabetic drugs can help prevent long-term complications of hyperglycemia in indi-viduals with T2DM. Considerable effort is being made to increase diabetes awareness and develop new pharmacological interventions to better treat the underlying causes of T2DM. This review provides a comprehensive overview of current knowledge in common genetic variants and novel targets for potential therapeutic use in T2DM and discusses recent advances in the pharmaceutical management of uncontrolled T2DM, including those currently in phase II and III development.