Type 2 Diabetes: Limitations of Current Therapies

Type 2 diabetes is a chronic disease associated with numerous microvascular and macrovascular complications. It affects millions of persons worldwide, posing an enormous socioeconomic burden. A growing body of evidence shows that comorbidities are greatly reduced when adequate glycemic control is achieved. Unfortunately, despite the variety of therapies currently available, the majority of patients do not achieve glycemic goals. Recent evidence demonstrating that diabetes progression can be stopped or even reversed with early and aggressive intervention, and the advent of therapies that address several of the mechanisms of diabetes pathophysiology, offers much promise for the future. This review article will identify the direct and indirect limitations of current type 2 diabetes therapies, and will explore new ways in which these limitations can be overcome. The prevalence of type 2 diabetes is relentlessly increasing as a result of today’s more sedentary lifestyles and increased obesity. In 2000, an estimated 171 million people worldwide had diabetes, and the number is projected to reach 366 million by 2030,1 resulting in high morbidity and a large economic burden. The pathophysiology of type 2 diabetes is progressive, characterized by decreased insulin sensitivity, deteriorating -cell function,2 and decreased incretin function.3 Decreased insulin function leads to chronic hyperglycemia (during fasting and postprandial periods) and acute glycemic fluctuations. These may be associated with microvascular and macrovascular complications caused by excessive protein glycation and activation of oxidative stress (Figure).4 The ultimate goal of type 2 diabetes treatment, therefore, should be to reduce all the components of dysglycemia. CAN DISEASE PROGRESSION