The evolution of basal insulin therapy over the past 100 years since the discovery of insulin is a testimony to the biomedical bench-to-bedside process, wherein incremental advances in the basic sciences are progressively translated over time into a series of enhancements in clinical care, each building upon the success of its predecessors. The emergence of recombinant DNA technology and the resultant biosynthesis of human insulin in the 1980s provided the critical capacity to bioengineer designer insulin analogues with pharmacokinetic and pharmacodynamic properties that can better mimic, although not fully replicate, the effects of endogenous insulin secretion. Through these efforts, basal insulin therapy has progressed over this time from first-generation analogues (glargine U-100, detemir) to second-generation analogues (glargine U-300, degludec) to ultra-long-acting formulations that are suitable for administration once weekly (icodec). Each iteration in this progression has represented a step closer towards the goal of replicating the continuous secretion of insulin that normally comprises the basal output of the pancreatic beta-cells between meals, during episodes of fasting and overnight. However, it may be that we may have reached the achievable limit in the context of an “open-loop” approach, such that only with the addition of closed loop control will we be able to achieve physiologic basal insulin replacement. In this review, we will examine the evolution of basal insulin therapy over the past 100 years and its implications for patient care and outcomes in current practice and the future.

中文翻译：

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100 多年来基础胰岛素治疗的持续发展及其对未来的承诺

自发现胰岛素以来，过去 100 年中基础胰岛素疗法的演变证明了生物医学从实验室到床边的过程，其中基础科学的渐进式进步随着时间的推移逐渐转化为一系列临床护理的改进，每一个都建立在其前辈的成功之上。1980 年代重组 DNA 技术的出现和由此产生的人胰岛素生物合成为生物工程设计胰岛素类似物提供了关键能力，这些胰岛素类似物具有药代动力学和药效学特性，可以更好地模拟（尽管不能完全复制）内源性胰岛素分泌的影响。通过这些努力，基础胰岛素治疗从第一代类似物（甘精胰岛素 U-100、地特胰岛素）发展到第二代类似物（甘精胰岛素 U-300、degludec) 到适合每周给药一次的超长效制剂 (icodec)。这一进程中的每一次迭代都代表着向复制胰岛素连续分泌的目标迈进了一步，胰岛素的连续分泌通常包括两餐之间、禁食和过夜期间胰腺β细胞的基础输出。然而，在“开环”方法的背景下，我们可能已经达到了可实现的极限，只有加上闭环控制，我们才能实现生理基础胰岛素替代。在这篇综述中，我们将研究过去 100 年来基础胰岛素治疗的演变及其对当前实践和未来患者护理和结果的影响。