Evaluation of alternative strategies for optimizing glycemia: progress to date

Adequate control of blood sugar has been repeatedly shown to translate into reductions in diabetic complications. Although insulin therapy in patients with type 2 diabetes can achieve and maintain near-normal glycemic goals associated with reductions in microvascular and macrovascular end points, it is often reserved for the later stages of management of these patients because of real or perceived concerns; these include fear and anxiety about worsening diabetes, failure of self-management, loss of quality of life, the pain of self-injection, and the possibility of multiple daily injections. Risks of hypoglycemia, weight gain, and cardiovascular disease may be concerns of physicians, but these risks are either manageable or, in the case of cardiovascular disease, unfounded. Taken together, the barriers to insulin therapy frequently compel physicians to consider it a treatment of last resort. Some of the more common barriers have been addressed through device options such as insulin pens and jet injectors, which may improve convenience but do not alleviate pain and discomfort. Transdermal delivery options using iontophoresis or ultrasound are in early stages of development, but methods based on transmucosal delivery-including buccal, nasal, and pulmonary routes-are further advanced. In particular, recent evidence shows that pulmonary forms of insulin are as safe and effective as rapid-acting injected insulin, and are well accepted by patients even over long-term periods of use. These innovative delivery systems may help overcome the barriers to insulin use.