Heinemann Lutz, Jacques Yves
Profil Institut für Stoffwechselforschung, Neuss, Germany.
J Diabetes Sci Technol. 2009 May 1;3(3):568-84. doi: 10.1177/193229680900300323.
Despite the availability of modern insulin injection devices with needles that are so sharp and thin that practically no injection pain takes place, it is still the dream of patients with diabetes to, for example, swallow a tablet with insulin. This is not associated with any pain and would allow more discretion. Therefore, availability of oral insulin would not only ease insulin therapy, it would certainly increase compliance. However, despite numerous attempts to develop such a "tablet" in the past 85 years, still no oral insulin is commercially available. Buccal insulin is currently in the last stages of clinical development by one company and might become available in the United States and Europe in the coming years (it is already on the market in some other countries). The aim of this review is to critically describe the different approaches that are currently under development. Optimal coverage of prandial insulin requirements is the aim with both routes of insulin administration (at least with most approaches). The speed of onset of metabolic effect seen with some oral insulin approaches is rapid, but absorption appears to be lower when the tablet is taken immediately prior to a meal. With all approaches, considerable amounts of insulin have to be applied in order to induce therapeutically relevant increases in the metabolic effect because of the low relative biopotency of buccal insulin. Unfortunately, the number of publications about clinical-experimental and clinical studies is surprisingly low. In addition, there is no study published in which the variability of the metabolic effect induced (with and without a meal) was studied adequately. In summary, after the failure of inhaled insulin, oral insulin and buccal insulin are hot candidates to come to the market as the next alternative routes of insulin administration.
尽管现在有了现代胰岛素注射装置，其针头非常锋利且细，几乎不会产生注射疼痛，但糖尿病患者仍梦想着，比如，能吞服含胰岛素的药片。这不会带来任何疼痛，还能更隐蔽。因此，口服胰岛素的出现不仅能减轻胰岛素治疗的负担，肯定还会提高依从性。然而，尽管在过去85年里人们多次尝试研发这样一种“药片”，但仍没有口服胰岛素上市。目前有一家公司正在对口腔胰岛素进行临床开发的最后阶段试验，未来几年可能会在美国和欧洲上市（在其他一些国家已上市）。这篇综述的目的是批判性地描述目前正在开发的不同方法。两种胰岛素给药途径（至少大多数方法）的目标都是最佳覆盖餐时胰岛素需求。一些口服胰岛素方法所产生的代谢效应起效速度很快，但在饭前立即服用药片时，吸收似乎较低。由于口腔胰岛素的相对生物效价较低，采用所有方法时都必须使用相当大量的胰岛素才能在代谢效应上产生与治疗相关的增加。不幸的是，关于临床实验和临床研究的出版物数量出奇地少。此外，还没有发表过充分研究（有或没有进餐情况下）所诱导的代谢效应变异性的研究。总之，在吸入胰岛素失败后，口服胰岛素和口腔胰岛素作为下一种替代胰岛素给药途径成为热门上市候选产品。
