The future of insulin therapy.

Although insulin therapy was already introduced one-hundred years ago, insulin formulations are still being refined to reduce the risk of hypoglycaemia and of other insulin side effects such as weight gain. This review summarises the available clinical data for some ongoing developments of new insulins and evaluates their potential for future insulin therapy. Once-weekly insulins will most likely be the next addition to the insulin armamentarium. First clinical studies indicate low peak-to-trough fluctuations with these insulins indicating the potential to achieve better glycaemic control or reduce hypoglycaemic events versus available basal insulins. Proof-of-concept has also been established for hepato-preferential and oral insulins; however, adverse effects and low bioavailability still need to be overcome. It will take much longer, before glucose-responsive "smart" insulins will be available. A first clinical study and numerous pre-clinical data show the potential, but also the challenges of designing an insulin that quickly reacts to blood glucose changes and prevents hypoglycaemia and pronounced hyperglycaemia. Nevertheless, it is reassuring that the search for better insulins has never stopped since its first use one-hundred years ago and is still ongoing. New developments have a high potential of further improving the safety and efficacy of insulin therapy in the future.