Lisco Giuseppe, De Tullio Anna, Guastamacchia Edoardo, Triggiani Vincenzo
Unit of Endocrinology, Metabolic Disease & Clinical Nutrition, Hospital "A. Perrino", Brindisi, Italy.
Section of Endocrinology, Local Health District of Bari, Bari, Italy.
Endocr Metab Immune Disord Drug Targets. 2021;21(4):626-646. doi: 10.2174/1871530320666200705211224.
New pieces of evidence suggest that combining basal insulin with glucagone-like peptide 1 receptor agonists (GLP-1RA) in patients with type 2 diabetes could promptly ameliorate glucose control and prevent both hypoglycemic events and unnecessary weight gain compared to more intensive insulin regimens. To review the efficacy/effectiveness and safety of fixed-ratio combinations of basal insulin and GLP- 1RA (FRCs). Authors searched PubMed/MEDLINE, ClinicalTrials.gov, Cochrane Library, and Google Scholar for freely available original articles, randomized clinical trials (RCTs), clinical reviews, and meta-analysis written in English until January 2020. FRCs provide significative reductions in HbA1c levels in both insulin-naïve (-1.4% to -2%) and insulin- experienced (-1.5% to -2%) type 2 diabetic patients with moderate glucose impairment. More patients achieved the recommended glycemic targets on FRCs compared to those on mono-therapy with basal insulin or GLP-1RAs. The intensification with FRCs results in better glycemic control compared to basal insulin at fasting as well as during the postprandial state. The frequency of hypoglycemia is similar or lower in patients treated with FRCs than in those on basal insulin alone at a similar dose. Weight trend can be variable, ranging from -2.7 to +2 Kg for iDegLira and -0.7 to -1.3 Kg for iGlar- Lixi. However, a lower weight gain is obtained with iDegLira compared to iDeg (-2.2 to -2.5 Kg), iGlar (-1.7 to -3.2 Kg), and basal-bolus (-3.6 Kg) as well as with iGlarLixi compared to iGlar (-1.4 Kg). FRCs should be considered to safely improve the metabolic control in type 2 diabetic patients with moderate glycemic impairment while on oral medications, basal oral regimen or GLP-1RAs. However, a few but significative pieces of evidence suggest that FRCs could be a safe and effective treatment instead of a low dose basal-bolus intensification for patients with mild or moderate glucose impairment in order to reduce the risk of hypoglycemia and unnecessary weight gain, and for simplifying treatment regimen as well.
新的证据表明，与强化胰岛素治疗方案相比，在2型糖尿病患者中联合使用基础胰岛素和胰高血糖素样肽1受体激动剂（GLP-1RA）可迅速改善血糖控制，并预防低血糖事件和不必要的体重增加。为了评估基础胰岛素与GLP-1RA固定比例复方制剂（FRCs）的疗效/有效性及安全性。作者检索了PubMed/MEDLINE、ClinicalTrials.gov、Cochrane图书馆和谷歌学术，查找截至2020年1月以英文撰写的可免费获取的原创文章、随机临床试验（RCT）、临床综述和荟萃分析。FRCs可使糖化血红蛋白（HbA1c）水平在初治（降低1.4%至2%）和曾接受胰岛素治疗（降低1.5%至2%）的中度血糖受损2型糖尿病患者中显著降低。与接受基础胰岛素或GLP-1RA单药治疗的患者相比，更多接受FRCs治疗的患者达到了推荐的血糖目标。与基础胰岛素相比，FRCs强化治疗在空腹及餐后状态下均能实现更好的血糖控制。在相似剂量下，接受FRCs治疗的患者低血糖发生频率与仅接受基础胰岛素治疗的患者相似或更低。体重变化趋势可能各不相同，德谷胰岛素利拉鲁肽（iDegLira）的体重变化范围为-2.7至+2千克，甘精胰岛素利司那肽（iGlar-Lixi）为-0.7至-1.3千克。然而，与德谷胰岛素（Deg，体重增加-2.2至-2.5千克）、甘精胰岛素（iGlar，体重增加-1.7至-3.2千克）和基础-餐时胰岛素方案（体重增加-3.6千克）相比，使用德谷胰岛素利拉鲁肽体重增加更低，与甘精胰岛素相比，使用甘精胰岛素利司那肽体重增加也更低（-1.4千克）。对于正在接受口服药物、基础口服治疗方案或GLP-1RA治疗的中度血糖受损2型糖尿病患者，应考虑使用FRCs来安全地改善代谢控制。然而，有一些但具有重要意义的证据表明，对于轻度或中度血糖受损患者，FRCs可能是一种安全有效的治疗方法，可替代低剂量基础-餐时胰岛素强化治疗，以降低低血糖风险和不必要的体重增加，并简化治疗方案。
