Concentrated insulins: History and critical reappraisal

• Published in: Journal of diabetes 2019-04, Vol.11 (4), p.292-300
• Main Authors: Heinemann, Lutz, Beals, John M., Malone, James, Anderson, James, Jacobson, Jennie G., Sinha, Vikram, Corrigan, Sheila M.
• Format: Article
• Language: English
• Subjects: concentrated insulins; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Disease management; Drug Compounding; history of insulin; History of medicine; Humans; Hypoglycemic Agents - administration & dosage; Insulin; insulin treatment; Insulins - administration & dosage; Therapeutic Equivalency; 浓缩胰岛素; 胰岛素历史; 胰岛素治疗
• ISSN: 1753-0393; 1753-0407
• DOI: 10.1111/1753-0407.12861

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. 摘要 最早上市的胰岛素是浓度≤ 10单位/mL的酸性粗制剂。自从20世纪20年代初以来,  通过生物工程、加工以及化学修饰不断地对胰岛素进行改良。如今,  大多数胰岛素制剂的浓度都是100单位/mL(U100)。然而,  如今还有更浓的胰岛素制剂(分别为200、300与500单位/mL;U200、U300与U500)。有一种倾向性的意见认为浓缩胰岛素都相类似,  既彼此相似,  也与对应的U100剂型相似,  但是却并非总是如此:有两种浓缩胰岛素,  即德谷胰岛素U200与赖脯胰岛素U200,它们生物等效于各自对应的U100剂型,  而常规人胰岛素U500与甘精胰岛素U300却不是这样。这些浓缩胰岛素的出现为患者提供了更多的特定治疗;但是它们也潜在地带来了困惑,  并且突显了处方医生与患者教育的需求。为了安全地使用这些浓缩胰岛素,  还需要有精准的专用胰岛素注射装置。虽然一些临床医生只对肥胖与严重胰岛素抵抗的患者使用浓缩胰岛素,  但是其他患者也将受益于与浓缩胰岛素相关的注射量减少,  或者受益于一些浓缩胰岛素的时间—作用曲线的改善。本综述的目的是加强我们对浓缩胰岛素历史研制过程的了解,  并且促进我们在临床实践中安全有效地使用浓缩胰岛素。 Highlights Since its first development, manufactured insulin has become increasingly concentrated. Concentrated insulins expand the options currently available to healthcare professionals in optimizing treatment for patients. Concentrated insulins provide changes in time‐action profiles, smaller injection volumes, and potentially fewer injections, which may improve patients’ experience with insulin and may lead to