The Role of the Kidney in Hyperglycemia A New Therapeutic Target in Type 2 Diabetes Mellitus

Background: Diabetes is a complex and chronic metabolic disease characterized by hyperglycemia due to defects in the secretion and action of insulin. Diabetes affects more than 8% of the US population. Type 2 diabetes mellitus (T2DM) is the most common form of diabetes and is associated with the development of a number of devastating microvascular complications, including retinopathy, neuropathy, and nephropathy. Diabetes is also a major risk factor for heart disease and stroke. Despite the availability of numerous treatment options for T2DM, glycemic control rates remain poor. Recently, there has been renewed interest in the role that the kidney plays in glucose homeostasis and the potential of the kidney as a therapeutic target in T2DM. Purpose: This article discusses the role of the kidneys and particularly sodium glucose cotransporter 2 in glucose homeostasis and the potential of inhibiting this transporter as a new treatment option for T2DM. Conclusions: The kidney plays an important role in glucose homeostasis by reabsorbing filtered glucose. In patients with T2DM, glucose reabsorption appears to be increased, potentially contributing to the hyperglycemia associated with this disease. Initial results from clinical trials with a number of sodium glucose cotransporter 2 inhibitors suggest that these compounds act to increase glucose excretion and decrease plasma glucose and body weight, and are generally well tolerated and do not appear to increase the risk of hypoglycemia. Clinical Implications: Sodium glucose cotransporter 2 inhibitors have a unique mechanism of action that is independent of insulin secretion or action. Results from ongoing and future clinical trials will determine whether this class of compounds becomes a treatment option for reducing hyperglycemia in patients with T2DM.