Nauck Michael, Wilhelm Birgit
Abteilung Diabetologie, Medizinische Klinik I, St. Josef-Hospital, Ruhr-Universität Bochum, Gudrunstr. 56, 44791, Bochum, Deutschland.
Novo Nordisk Pharma GmbH, Mainz, Deutschland.
MMW Fortschr Med. 2017 Jun;159(Suppl 5):7-15. doi: 10.1007/s15006-017-9803-2. Epub 2017 Jun 22.
In 2015, the combination of basal insulin and GLP-1 receptor agonist (RA) was incorporated into the guideline recommendations for type 2 diabetes as an option for the last escalation step. The two antidiabetics to be injected subcutaneously are complementary regarding their respective main effects and limitations. Basal insulin is predominantly active between meals and in the fasting state, whereas the main action of GLP-1 RA consists in preventing an excessive postprandial blood glucose increase. Moreover, GLP-1 RA is characterised by a low intrinsic risk of hypoglycaemia, body weight reduction and a positive impact on cardiovascular risk factors. Unlike GLP-1 RA, no upper dose limits are defined for basal insulin. However, initiation of insulin therapy is associated with disadvantages in terms of hypoglycaemia and weight increase. Therefore, patients achieving their treatment goals with GLP-1 RA alone are better treated without insulin.
In a review, study results on combinations of basal insulin and GLP-1-RA versus comparative therapies are presented.
Most of the studies were carried out in patients pre-treated with basal insulin. The add-on of GLP-1 RA was commonly associated with significant reductions of body weight and also resulted in additional HbA reductions compared with an increase of the basal insulin dose. The add-on of a short acting insulin to an existing basal insulin therapy enabled similar HbA reductions to the add-on of a GLP-1 RA, but simultaneously increased the number of episodes of hypoglycaemia and might lead to more unfavourable body weight developments. A fixed combination of insulin degludec and liraglutide (IDegLira) showed an effective and rather steady blood glucose reduction in a 24-hour interval vs. basal insulin or GLP-1 RA alone.
Combinations of basal insulin and a GLP-1 RA improve glycaemic control in many patients with type 2 diabetes without any significant increase of the risk of hypoglycaemia and without weight gain, especially compared to a dose increase of the basal insulin or add-on of a short-acting insulin.
2015年，基础胰岛素与胰高血糖素样肽-1受体激动剂（RA）的联合用药被纳入2型糖尿病指南推荐，作为最后升级步骤的一种选择。这两种皮下注射的抗糖尿病药物在各自的主要作用和局限性方面具有互补性。基础胰岛素主要在餐间和空腹状态下起作用，而胰高血糖素样肽-1受体激动剂的主要作用在于防止餐后血糖过度升高。此外，胰高血糖素样肽-1受体激动剂的特点是低血糖的内在风险低、体重减轻以及对心血管危险因素有积极影响。与胰高血糖素样肽-1受体激动剂不同，基础胰岛素没有设定剂量上限。然而，胰岛素治疗的起始在低血糖和体重增加方面存在劣势。因此，仅使用胰高血糖素样肽-1受体激动剂就能实现治疗目标的患者无需使用胰岛素治疗效果更佳。
在一篇综述中，展示了基础胰岛素与胰高血糖素样肽-1受体激动剂联合用药与对照疗法的研究结果。
大多数研究是在接受基础胰岛素预处理的患者中进行的。添加胰高血糖素样肽-1受体激动剂通常与体重显著减轻相关，并且与增加基础胰岛素剂量相比，还能进一步降低糖化血红蛋白（HbA）。在现有的基础胰岛素治疗中添加短效胰岛素能够实现与添加胰高血糖素样肽-1受体激动剂相似的糖化血红蛋白降低效果，但同时会增加低血糖发作次数，并且可能导致更不利的体重变化。德谷胰岛素和利拉鲁肽的固定复方制剂（IDegLira）在24小时内显示出有效且相当稳定的血糖降低效果，优于单独使用基础胰岛素或胰高血糖素样肽-1受体激动剂。
基础胰岛素与胰高血糖素样肽-1受体激动剂的联合用药可改善许多2型糖尿病患者的血糖控制，且低血糖风险无显著增加，体重也不增加，特别是与增加基础胰岛素剂量或添加短效胰岛素相比。
