Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial

In this post hoc analysis of the randomized controlled LixiLan-O trial in insulin-naive patients with type 2 diabetes mellitus (T2DM) not controlled with metformin, with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed-ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: group 1) baseline HbA1c ≥9% (n = 134); group 2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725). Treatment with iGlarLixi resulted in significantly greater reduction in least squares mean HbA1c compared to treatment with iGlar or Lixi alone in both subgroups (group 1: 2.9%, 2.5%, 1.7% and group 2: 1.5%, 1.2%, 0.7%, respectively). Target HbA1c less than 7% was achieved in more than 70% of patients using iGlarLixi in both subgroups, while mitigating the weight gain observed with use of iGlar alone. Rates of hypoglycaemic events were low overall. These results suggest that treatment with iGlarLixi achieves superior glycaemic control compared to treatment with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or in those inadequately controlled with two OADs.     

Treatment intensification in patients with inadequate glycemic control on basal insulin: rationale and clinical evidence for the use of short‐acting and other glucagon‐like peptide‐1 receptor agonists

A substantial proportion of patients with type 2 diabetes mellitus do not reach glycemic targets, despite treatment with oral anti‐diabetic drugs and basal insulin therapy. Several options exist for treatment intensification beyond basal insulin, and the treatment paradigm is complex. In this review, the options for treatment intensification will be explored, focusing on drug classes that act via the incretin system and paying particular attention to the short‐acting glucagon‐like peptide‐1 receptor agonists exenatide and lixisenatide. Current treatment guidelines will be summarized and discussed. © 2016 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.     

利司鲁肽治疗2型糖尿病的系统评价

目的：系统评价新型GLP-1受体激动剂利司鲁肽治疗2型糖尿病的疗效与安全性。方法：电子检索中英文数据库中有关利司鲁肽治疗2型糖尿病的随机临床试验（RCT）,时限至2016年5月;2位研究者独立评阅文献,并筛选及予以质量评价;采用RevMan 5.0软件对各效应指标进行Meta分析。结果：纳入7篇RCT,文献质量评价均属低偏倚风险,2型糖尿病患者共计2 089例,其中试验组（利司鲁肽治疗）1 128例,对照组（安慰剂）961例,Meta分析结果显示,于治疗周期末,2组HbA_1c水平、HbA_1c达标率（≤6.5%）有统计学差异（P<0.05）,FPG水平变化无统计学差异（P>0.05）,恶心、呕吐、胃肠功能紊乱、低血糖反应及因不良事件（AE）退出治疗的发生率有统计学差异（P<0.05）,腹泻、头痛、头晕、鼻咽炎及SAE发生率无统计学差异（P>0.05）。结论：利司鲁肽对2型糖尿病患者血糖水平有较好控制作用,但其不良反应发生率仍有较大差异,尚需更多大样本、多中心随机临床试验予以证实。     

GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta-analysis including the REWIND and PIONEER 6 trials

A meta-analysis of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) and placebo concerning cardiorenal outcomes in patients with type 2 diabetes (T2D) is presented. An electronic search without language restrictions up to June 15, 2019 was conducted to determine eligible trials. A meta-analysis of available trial data was undertaken, using a random-effects model to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Data from seven CVOTs, comprising 56 004 patients (68.9% with established cardiovascular disease) were included. GLP-1RA reduced major cardiovascular events (MACE) by 13% (HR, 0.87; 95% CI, 0.80–0.96; P = 0.011) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (CVD) (P = 0.220). GLP-1RA also reduced the risk of cardiovascular death by 12%, of non-fatal stroke by 16%, of hospitalization for heart failure by 9%, of all-cause mortality by 11%, and the broad composite kidney outcome by 17%; the latter appeared to be driven only by a reduction in macroalbuminuria (HR, 0.76 [0.68–0.86]; P = 0.003). GLP-1RAs have moderate benefits concerning MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also robustly reduce the incidence of macroalbuminuria, without affecting the progression of diabetic renal disease.     

利西拉肽对阿尔茨海默病保护作用机制的研究进展

近年来,越来越多的临床和实验数据表明2型糖尿病与阿尔茨海默病之间关系密切。2型糖尿病和阿尔茨海默病具有共同的病理生理特征:β淀粉样蛋白沉积、tau蛋白过磷酸化和葡萄糖合成酶3活性增加。研究发现2型糖尿病患者患阿尔茨海默病的风险与正常人比较有增加的趋势。对阿尔茨海默病动物模型脑组织进行研究,结果表明应用胰高血糖素样肽1类似物治疗后,脑内胰岛素抵抗得到改善,四羟壬烯酸、丙二醛等氧化应激指标显著减少,而其他病理特征有逆转的趋势,特别是新型的胰高血糖素样肽1受体激动剂利西拉肽作用更显著,且不良反应事件更少。最新文献证实利西拉肽具有神经保护作用,可用于阿尔茨海默病的治疗。文中就利西拉肽在阿尔茨海默病中的作用做一综述。     

Fixed-ratio combination therapy for type 2 diabetes: the top ten things you should know about insulin and glucagon-like peptide-1 receptor agonist combinations

Many individuals with type 2 diabetes (T2D) will eventually require insulin therapy to help achieve and maintain adequate glycemic control. However, the use of insulin can be associated with adverse effects such as hypoglycemia and weight gain, and in some patients the addition of insulin to treatment regimens is often still insufficient to achieve target glycemic control. Combining basal insulin with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of patients with T2D has been demonstrated to be effective and well tolerated, while mitigating many of the adverse events associated with giving either of these drug classes alone. Two titratable, fixed-ratio combination therapies, iGlarLixi and IDegLira, that combine basal insulin and a GLP-1 RA in a once-daily subcutaneous injection are currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with T2D. The fixed-ratio combination iGlarLixi combines insulin glargine 100 Units/mL with lixisenatide, while IDegLira combines insulin degludec 100 Units/mL with liraglutide. While these new fixed-ratio combinations contain antihyperglycemic medications that are familiar to most health care providers, there are many questions relating to their use when formulated as a fixed-ratio combination therapy. This article discusses the ‘top 10’ considerations that health care providers should know about these novel combination therapies as these agents begin to gain an increasing presence in clinical practice.