Hepatic dysfunction and/or renal impairments in older adults may limit the use of many glucose-lowering agents. Table 1 Glucose-lowering effects, advantages, and disadvantages of various glucose-lowering agents in older adults with type 2 diabetes Open in a separate window GI, gastrointestinal; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1. aExpected reduction in HbA1c when used as a monotherapy. Metformin Metformin is currently recommended as the first line drug therapy for the management of diabetes in many guidelines because of proven effectiveness in lowering blood glucose, a relatively low risk of hypoglycemia, and low cost [33]. elderly diabetics with cognitive impairment are at three times higher risk of severe hypoglycemia requiring health services Rabbit polyclonal to DCP2 [20]. They are also at increased risk of major cardiovascular events and death [21]. Depression Depression is highly prevalent in older adults with diabetes. Approximately 30% of people with diabetes have depressive symptomatology, 10% have major depression, and recent studies have shown that people with diabetes have two-fold increased odds of depression compared with individuals without diabetes [22-25]. The coexistence of diabetes and major depression is associated with increased health care use, increased health care costs, and adverse health outcomes for diabetes [24,26]. Furthermore, depression is associated with hyperglycemia and an increased risk for diabetic complications, and relief of depression is associated with improved glycemic control. Depression is also a major contributor to functional disability and quality of life. Functional disability in depressed patients is thought to result from decreased physical activity, decreased likelihood of seeking medical care, and increased susceptibility to disease [22,27]. Healthcare providers should be aware of the frequent coexistence of psychiatric conditions, such as depression or other psychiatric conditions, in elderly patients with diabetes. It is important to screen all diabetic elderly patients for mental health issues as these may interfere with self-care and the overall management of diabetes. mTOR inhibitor-2 Recognition and management of psychiatric disorders will help to optimize diabetes management. Good diabetes control can also reduce mental health complications in these patients [28]. TREATMENT GOALS IN OLDER ADULTS WITH DIABETES The goals of diabetes management in older adults should be set according to the motivation, combined diseases, presence of complications, resources, support system, and life expectancy of each individual patient [7]. Most previous guidelines have failed to provide any specific recommendation for older adults with diabetes. The California Healthcare Foundation/American Geriatric Society Panel on Improving Care for Elders with Diabetes suggested that a reasonable goal for hemoglobin A1c (HbA1c) in relatively healthy elderly with good functional status should mTOR inhibitor-2 be 7% or lower. For frail adults, persons with life expectancy of less than 5 years, and others in whom the risks of intensive glycemic control appear to outweigh the benefits, a less stringent target of 8% was recommended [4]. It is less likely that the use of intensive therapy to target near normoglycemia (HbA1c 6.0%) will show benefits among older adults with diabetes. Elderly diabetics may have long duration of diabetes, previous history of cardiovascular diseases, or multiple cardiovascular risk factors, including hypertension, dyslipidemia, and many other comorbid conditions. All of the aforementioned conditions limit the benefits of intensive therapy in older adults with diabetes. On the contrary, as demonstrated in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, intensive management of hyperglycemia targeting HbA1c 6% may increase death from any cause (hazard ratio [HR], 1.19; 1.03 to 1 1.38, em P /em =0.02) and death from cardiovascular causes (HR, 1.29; 1.04 mTOR inhibitor-2 to 1 1.60, em P /em =0.02) [29,30]. Similarly, the Veterans Affairs Diabetes Trial (VADT) mTOR inhibitor-2 and the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial failed to show benefits in cardiovascular endpoints [31,32]. Therefore, intensive management targeting normoglycemia should be avoided in older adults. At a minimum, intensive control should be performed with great caution in older adults with diabetes. GLUCOSE-LOWERING AGENTS IN OLDER ADULTS WITH DIABETES In older adults with diabetes, the choice of anti-hyperglycemic agents should be based not only on efficacy, but drug safety (Table 1). Older.