21411_New Pathways to GLYCEMIC CONTROL: Focus on the Kidney

Presentations by Jay Shubrook, DO (Chair), Eugene Cersosimo, MD, PhD, and Robert Henry, MD. discussing the role of glucose regulation and SGLT 2 inhibitors in antihyperglycemic therapy

The kidney plays a major role in the regulation of glucose, reabsorbing virtually all of the glucose that filters through the renal glomeruli tubules. In non-diabetic individuals, the transport maximum for glucose is well above the filtered glucose load; therefore, the kidney conserves this critical energy source. However, in hyperglycemic individuals, this adaptive mechanism becomes maladaptive. The diabetic kidney appears to have an increased transport maximum for glucose, thereby minimizing glucosuria and exacerbating the hyperglycemia. In this manner, the kidneys contribute to the pathophysiologic process of hyperglycemia in patients with diabetes. In hyperglycemic individuals, when the transport maximum is exceeded, large amounts of glucose are excreted in the urine even though the renal tubules continue to function normally.

Sodium-glucose cotransporters (SGLTs) are responsible for active transport of glucose across the proximal convoluted tubule cells of the kidney, and SGLT 2 is thought to account for approximately 90% of reabsorbed glucose. SGLT 2 inhibitors have been developed as insulin independent treatments for type 2 diabetes. The rationale for these agents is that inducing or enhancing glucosuria will decrease plasma glucose levels and reduce glucose toxicity, as well as potentially produce additional benefits.

Interpreting the clinical data and the role of SGLT 2 inhibitors in patient management is an unmet clinical need, given 1) the overall complexities of antihyperglycemic therapy with numerous medication classes available for use and 2) several factors to consider when selecting an antihyperglycemic agent. In this program, diabetes experts Dr. Jay Shubrook (Program Chair), Dr. Eugenio Cersosimo, and Dr. Robert Henry will explore glucose regulationby the kidney, assess efficacy and safety data with SGLT 2 inhibitors and their role in treatment, and provide insights into effective use of combination antihyperglycemic therapy for achieving glycemic control in patients with type 2 diabetes.

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