New concepts in diabetes: how multihormonal regulation can improve glycemic control

It is estimated that 18.2 million Americans are currently living with diabetes, a disease that continues to place significant economic burdens on patients, their families, health plans, systems, and society. Recent data from the American Diabetes Association indicates that the annual direct and indirect costs of diabetes are rapidly increasing. Improved glycemic control--which has been repeatedly demonstrated to reduce the risk of developing microvascular complications and is likely to reduce the risk of macrovascular complications associated with type 1 and type 2 diabetes--has the potential to improve quality of life and reduce health care expenditures. However, despite recent advances in oral antidiabetic agents and insulin management (e.g., development of rapid- and long-acting insulin analogs and continuous subcutaneous insulin infusion [CSII]), only a portion of the patient population is able to achieve the goals for glycemic control recommended by the American Diabetes Association, the American College of Endocrinology, and other guideline-setting organizations. Moreover, improved glycemia achieved with present therapeutic modalities may be associated with the risk of hypoglycemic events and undesired weight gain. The latter can negatively affect plasma lipids, blood pressure, and therapy adherence. New research into the pathophysiology of diabetes indicates that multiple hormones--not just insulin and glucagon but amylin, GLP-1 (a glucagon-like peptide), and others--are involved in the regulation of plasma glucose levels, providing insight into why even insulin is often ineffective in helping patient with diabetes achieve their glycemic goals. The use of analogs of these newly recognized, important glucoregulatory hormones; agents that delay the degradation of the hormones and therefore raise their concentration; and/or agents that bind to their receptors may facilitate achievement of improved glycemia. One of these agents, pramlintide, represents the first new potential antihyperglycemic agent for the treatment of type 1 diabetes since insulin was introduced more than 80 years ago. There is substantial potential for these agents to improve glycemic control and patient outcomes and to reduce the personal, societal, and economic burdens of diabetes. Some of these novel multihormonal glucoregulatory therapies will likely soon become important components of the diabetes armamentarium. It is therefore important that managed care pharmacy decision makers learn about them.