Concentrated insulins: History and critical reappraisal.

The earliest marketed insulins were crude acidic formulations with concentrations of ≤10 units/mL. Since the early 1920s, insulins have improved continually, via bioengineering, process, and chemical modifications. Today, most insulin formulations have a concentration of 100 units/mL (U100). However, more concentrated insulin formulations (200, 300, and 500 units/mL; U200, U300, and U500, respectively) are also available. There is a tendency to assume that concentrated insulins are similar, both to each other and to their U100 counterparts, but this is not always the case: two concentrated insulins, namely insulin degludec U200 and insulin lispro U200, are bioequivalent to their U100 counterparts, whereas regular human insulin U500 and insulin glargine U300 are not. The advent of these concentrated insulins offers greater opportunities to provide tailored therapy for patients; it also introduces potential confusion, and highlights the need for prescriber and patient education. Precise and accurate dedicated insulin delivery devices are also necessary for the safe use of these concentrated insulins. Although some clinicians only use concentrated insulin with obese and severely insulin-resistant patients, other patients would also benefit from the reduced injection volume associated with concentrated insulins, or the modified time-action profile of some concentrated insulins. The aim of this review is to enhance understanding of the historic development and the safe and effective use of concentrated insulins in clinical practice.