Incretin-based therapies in complex patients: practical implications and opportunities for maximizing clinical...

Elderly patients and patients with renal impairment present unique challenges in the management of diabetes mellitus. Impaired renal function is a common comorbidity (or complication) associated with type 2 diabetes, as well as a complicating factor in the treatment of the disease. Renal insufficiency, which can result in elevated plasma concentrations of pharmaceutical agents, may preclude the use of some antihyperglycemic medications and require that the dosages of others be reduced. Failure to select and dose medications carefully in these patients may increase the risk of hypoglycemia and other adverse effects. For example, elevated plasma concentrations of some sulfonylureas may increase the risk of hypoglycemia. Because patients with chronic renal insufficiency tend to retain fluids, treatment with a thiazolidinedione--a class of agents associated with fluid retention--may exacerbate the risk of edema. Older patients with type 2 diabetes--like patients with renal insufficiency an important and populous subgroup--also have issues with therapy selection and dosing regimens. As a result of the effects of aging on kidney function, older patients may also be subject to elevated plasma levels with consequent additional risk of hypoglycemia and other adverse events. Because older patients tend to be treated with multiple medications for multiple comorbidities, it becomes challenging to design regimens that avoid or reduce the risk of drug-drug interactions. For both older patients and patients with chronic renal insufficiency, the most important drug-related adverse effect to avoid is hypoglycemia. Accordingly, incretin-based agents have an advantage because they are unlikely to cause hypoglycemia.