The need for better insulin therapy.

Insulin replacement therapy corrects a core defect of diabetes pathophysiology. Since its introduction as a therapeutic modality almost 100 years ago, insulin therapy has undergone remarkable changes in purity and ability to provide more physiologic control of blood glucose levels. With glucose-lowering potential limited only by risks of hypoglycaemia, which remains the major limitation in our ability to achieve glycaemic goals, insulin replacement therapy remains a cornerstone of therapy. Major progress in reducing the risks of hypoglycemia has occurred with the development of insulin analogs. This review article briefly chronicles the evolution of insulin replacement strategies, highlighting both challenges in pharmaceutical development and patient acceptance, underscoring achievements, as well as denoting what improvements are still needed.