專題討論4:糖尿病、高血脂及心血管疾病

S4-2
糖尿病用藥與心血管疾病的最新實證
王治元
台大醫院內科部 台大醫學院內科

  Type 2 diabetes mellitus, one of the most common chronic diseases in the world, may remain undetected for many years. However, medical providers often treat such disease in advanced stage, and vascular complications have already established in the majority of patients. Macrovascular complications are mainly represented by atherosclerotic diseases. On the other hands, diabetes-related microvascular disease such as retinopathy and nephropathy are major causes of deteriorating life quality and handicap. Hyperglycemia and insulin resistance play the pivotal roles in the development of atherosclerosis and its complications. Many evidence-based data suggest that metabolic abnormalities may result in overproduction of reactive oxygen species (ROS). Therefore, ROS induces endothelial dysfunction and inflammation, could the cause in precipitating diabetic vascular disease. A better understanding of ROS-generating pathways could provide the basis to develop novel therapeutic strategies against vascular complications in translational medicine. We could use knowledge from the connection between basic science and clinical practice to improve the deteriorated course.
  Anti-diabetic medications of oral and injected pattern were developed for more than many decades. Efficacy of glycemic control was always emphasized until UDGP and UKPDS study. Early intervention with consideration of drug safety issues was discussed after completing above studies. Biguanides was firstly discussed due to the possible lactic acidosis and limitation in renal insufficiency, and sulfonylurea was later mentioned about its hypoglycemic potential and risk, but prominent gloucose lowering efficacy. TZD was developed since early 1990’s, but the issue of probable cardiovascular risk or bladder cancer was preliminarily clarified until 2013 and 2014, respectively. Recently, two new categories of anti-diabetic medications were delicately evaluated, including DPP-4 inhibitors and SGLT-2 inhibitors. The non-inferiority study of DPP-4 inhibitors, such as SAVOR, EXAMINE, and TECOS, established the safety issues of this new category, however, heart failure issue was still under further observed after SAVOR study. On the other hand, empagliflozin, one of the SGLT-2 inhibitors, completed EMPA-REG/CANVAS studies to prove SGLT-2 inhibitors could statistically reduced cardiovascular mortality and heart failure with uncertain mechanism. However, SGLT-2 inhibitors still should face the issue of euglycemic ketosis prone complication and need duplicating its real efficacy to reduce CV mortality via second prospective study. We, the diabetologists, in 21th century, are so lucky having so many effective medications. But, how choosing the correct medications for the right T2DM patients with or without atherosclerotic cardiovascular diseases still needs to be clarified.