Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.
Handb Exp Pharmacol. 2022;274:415-438. doi: 10.1007/164_2021_574.
Since the first use of insulin 100 years ago, there have been marked improvements in diabetes therapy including, but not limited to, the development of oral antidiabetic agents (OADs), incretin mimetics and insulin analogues. Still, there are substantial shortcomings in diabetes therapy: the blood-glucose lowering effect of OADs is often limited, incretin mimetics often induce gastrointestinal side effects and insulins still induce hypoglycaemia and weight gain in many patients.This review evaluates on-going developments of antidiabetic drugs for their potential for future therapy focussing on injectable therapies. Recent data from dual agonists, in particular tirzepatide, a combination of GIP- and GLP-1 receptor agonists, show unprecedented reductions in HbA1c, body weight and cardiovascular risk factors. Once-weekly administrations of incretin mimetics open up the potential of a combination with once-weekly insulins that have been shown to have low peak-to-trough fluctuations. Eventually, it might be feasible to administer incretins and insulins (combinations) orally. While this has already been achieved for incretins, there are still some challenges for the oral application of insulin. Nevertheless, many promising data of novel antidiabetic drugs clearly indicate that therapy of people with diabetes will become easier, safer and more efficacious in the next years.
自 100 年前首次使用胰岛素以来，糖尿病治疗取得了显著进展，包括但不限于口服抗糖尿病药物（OADs）、肠促胰岛素类似物和胰岛素类似物的开发。尽管如此，糖尿病治疗仍存在很大的不足：OAD 的降血糖作用往往有限，肠促胰岛素类似物常引起胃肠道副作用，而胰岛素仍会引起许多患者低血糖和体重增加。本综述评估了正在开发的抗糖尿病药物，评估其未来治疗的潜力，重点是注射治疗。最近来自双重激动剂的数据，特别是胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素多肽（GIP）双重受体激动剂替西帕肽，显示出史无前例的 HbA1c、体重和心血管风险因素降低。每周一次给予肠促胰岛素类似物，为每周一次给予胰岛素的联合治疗开辟了可能性，已证明这种联合治疗具有较低的峰值到谷值波动。最终，有可能实现肠促胰岛素和胰岛素（联合）的口服给药。虽然这已经在肠促胰岛素上实现，但胰岛素的口服应用仍存在一些挑战。然而，许多新型抗糖尿病药物的有前景的数据清楚地表明，在未来几年，糖尿病患者的治疗将变得更容易、更安全、更有效。
