Julio Rosenstock, Rattan Juneja, John M Beals, Julie S Moyers, Liza Ilag, Rory J McCrimmon
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引用次数: 0
摘要
基础胰岛素仍然是许多糖尿病患者治疗的重要组成部分。为了延长胰岛素制剂的持续时间,人们首先开发了需要在注射前均质化的悬浮液。这些胰岛素需要每天注射一次或两次,导致胰岛素暴露量差异很大,对血糖的影响难以预测。过去二十年来,长效、可溶性基础胰岛素类似物取得了进展,其药代动力学暴露时间更长且变化更小,从而提高了其疗效和安全性,尤其是减少了夜间低血糖的发生。然而,由于低血糖问题和治疗负担等多种原因,每日一次基础胰岛素治疗的依从性和持续性仍然很低。可溶性基础胰岛素的暴露曲线更长、更平滑,可减少药效学变异性,从而有可能减少低血糖的发生,其疗效与每日一次基础胰岛素相似,可简化给药方案,提高治疗依从性。胰岛素 icodec(诺和诺德)和胰岛素 efsitora alfa(基础胰岛素 Fc [BIF],礼来公司)就是这样两种设计为每周给药一次的胰岛素,它们有可能进一步推动基础胰岛素的替代。Icodec和efsitora的2期临床试验以及icodec项目3期的数据表明,每周一次的胰岛素可提供与每日一次的类似物相当的血糖控制效果,而且发生低血糖的风险相似。本手稿详细介绍了用于开发每周一次基础胰岛素的技术。它强调了这些每周胰岛素的临床原理和潜在优势,同时也讨论了这些分子在临床实践中可能带来的局限性和挑战。
The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa.
Basal insulin continues to be a vital part of therapy for many people with diabetes. First attempts to prolong the duration of insulin formulations were through the development of suspensions that required homogenization prior to injection. These insulins, which required once- or twice-daily injections, introduced wide variations in insulin exposure contributing to unpredictable effects on glycemia. Advances over the last 2 decades have resulted in long-acting, soluble basal insulin analogues with prolonged and less variable pharmacokinetic exposure, improving their efficacy and safety, notably by reducing nocturnal hypoglycemia. However, adherence and persistence with once-daily basal insulin treatment remains low for many reasons including hypoglycemia concerns and treatment burden. A soluble basal insulin with a longer and flatter exposure profile could reduce pharmacodynamic variability, potentially reducing hypoglycemia, have similar efficacy to once-daily basal insulins, simplify dosing regimens, and improve treatment adherence. Insulin icodec (Novo Nordisk) and insulin efsitora alfa (basal insulin Fc [BIF], Eli Lilly and Company) are 2 such insulins designed for once-weekly administration, which have the potential to provide a further advance in basal insulin replacement. Icodec and efsitora phase 2 clinical trials, as well as data from the phase 3 icodec program indicate that once-weekly insulins provide comparable glycemic control to once-daily analogues, with a similar risk of hypoglycemia. This manuscript details the technology used in the development of once-weekly basal insulins. It highlights the clinical rationale and potential benefits of these weekly insulins while also discussing the limitations and challenges these molecules could pose in clinical practice.
期刊介绍:
Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.