The effect of baseline characteristics on clinical efficacy of liraglutide in patients treated with high‐dose insulin

In patients requiring high‐dose insulin treatment, a randomized, double‐blind, placebo‐controlled study showed that liraglutide improved glycaemic control and treatment satisfaction while promoting weight loss. We performed a post hoc analysis to evaluate if patients’ baseline characteristics impact the efficacy of liraglutide, and which outcomes correlate with treatment satisfaction. We used regression analysis to model the change in HbA1c and weight, with treatment assignment and baseline characteristics [HbA1c, age, body mass index (BMI), total daily dose (TDD) of insulin, duration of insulin treatment, and type of insulin regimen] as independent variables. Improvement in HbA1c was best predicted by treatment with liraglutide, followed by higher baseline HbA1c, BMI and age. Changes in weight were only associated with liraglutide treatment, independent of all baseline characteristics. Improvement in HbA1c was the only significant predictor of improvement in treatment satisfaction, while weight loss, change in TDD of insulin and rate of hypoglycaemia did not influence treatment satisfaction. In patients treated with high‐dose insulin, liraglutide significantly improved glycaemic control and led to weight loss regardless of patients’ baseline characteristics. Improvement in HbA1c was the most important predictor of patients’ treatment satisfaction.     

Liraglutide Protects Neurite Outgrowth of Cortical Neurons Under Oxidative Stress though Activating the Wnt Pathway

Background

Neurogenesis including neurite outgrowth is important for brain plasticity under physiological conditions and in brain repair after injury. Liraglutide has been found to have neuroprotective action in the risk of central nervous system disease. However, the effect and the potential mechanism of liraglutide-induced neurite outgrowth in primary cortical neurons under oxidative stress remain poorly documented.

利拉鲁肽对脲链佐菌素诱导阿尔茨海默病大鼠认知功能及Tau蛋白磷酸化的影响

目的：探讨利拉鲁肽对脲链佐菌素（STZ）诱导阿尔茨海默病（AD）大鼠认知功能及Tau蛋白磷酸化的影响。方法：Wistar雄性大鼠24只,随机分为空白对照组、假手术组、模型组和治疗组,每组6只,采用单次右侧脑室注射STZ（3 mg/kg）诱导AD大鼠,14 d后连续4周皮下注射利拉鲁肽干预;利用Morris水迷宫实验检测大鼠认知功能改变,利用免疫组织化学法和Western blot法检测Ser396位点磷酸化的Tau蛋白表达。结果：Morris水迷宫实验结果显示,与空白对照组相比,假手术组大鼠的逃逸潜伏期和穿越平台次数差异无统计学意义（P>0.05）;与假手术组相比,模型组大鼠逃逸潜伏期和穿越平台次数增加（P<0.05）;与模型组相比,利拉鲁肽治疗组大鼠逃逸潜伏期和穿越平台次数减少（P<0.05）。免疫组化和Western blot检测结果显示,模型组大鼠海马组织中Ser396位点磷酸化的Tau蛋白表达增加（P<0.05）,经利拉鲁肽干预后表达减少（P<0.05）。结论：利拉鲁肽能改善STZ诱导的AD大鼠空间学习记忆能力的损伤,降低大鼠海马区Ser396位点磷酸化的Tau蛋白表达。     

不同剂量利拉鲁肽治疗肥胖2型糖尿病的疗效观察

目的 观察利拉鲁肽在初诊的肥胖2型糖尿病患者中的疗效.方法 初诊的肥胖2型糖尿病患者,分别予以利拉鲁肽1.2 mg、1.8 mg皮下注射,每日1次,连续3个月.治疗前后观察患者HbA1C、血糖、体重、收缩压及LDL的变化.结果 治疗后,患者HbA1C、血糖、体重、收缩压、血脂较治疗前均有改善.结论 利拉鲁肽作为肥胖的2型糖尿病患者的初始治疗安全有效.     

利拉鲁肽治疗超重或肥胖超药品说明书用法的循证评价

目的运用循证药学的方法评价利拉鲁肽用于治疗超重或肥胖的临床证据,为超说明书用药循证评价提供参考。方法系统检索Pub Med、EMBASE、Cochrane Library、CNKI、万方数据库,国外药品说明书及MICROMEDEX■循证数据库,由两名评价者独立的根据纳入排除标准筛选文章,评价文献质量,提取数据并分析。结果共纳入FDA与EMA药品说明书、循证数据库MICROMEDEX■、5项国内外指南与6篇系统评价/Meta分析。利拉鲁肽与安慰剂相比可以显著降低肥胖患者的体重和BMI、提高体重减轻至少5%的患者比例。安全性方面利拉鲁肽由于不良反应而停止治疗的比率显著高于安慰剂,其中胃肠道不良反应发生率较高。结论利拉鲁肽用于治疗BMI>27 kg·m^-2合并至少一项肥胖并发症、或者BMI>30 kg·m^-2的单纯性肥胖的患者具有较好的疗效,但是需要注意患者胃肠道不良反应。     

Can a fixed-ratio combination of insulin degludec and liraglutide help Type 2 diabetes patients to optimize glycemic control across the day?

‘IDegLira’ combines insulin degludec (IDeg) with the glucagon-like peptide-1 analog liraglutide (Lira) at a ratio of 1 unit IDeg to 0.036 mg Lira. The two components have complementary therapeutic actions for the treatment of Type 2 diabetes. Studies have shown that combinations of basal insulin with glucagon-like peptide-1 receptor agonists can be clinically successful, lowering elevated blood glucose with a low risk of hypoglycemia and weight gain. IDegLira is being assessed in a series of studies (two already published), which provide insights into its clinical utility in previously insulin-naive patients and those failing to achieve good glycemic control on a basal-only insulin regimen. This article critically examines the available data to assess the product’s likely clinical profile.     

The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials

It is unknown if the cardioprotective and renal effects of glucagon-like peptide-1 receptor agonists are consistent across blood pressure (BP) categories in patients with type 2 diabetes and at high risk of cardiovascular events. Using data from the LEADER (9340 patients) and SUSTAIN 6 (3297 patients) trials, we evaluated post hoc the cardiorenal effect of liraglutide and semaglutide on major adverse cardiovascular events (MACE) and nephropathy by baseline BP categories using a Cox proportional hazards model (treatment and subgroup as factors; adjusted for cardiorenal risk factors). Data from the two trials were analysed separately. In the LEADER and SUSTAIN 6 trials, the prevalence of stage 1 hypertension was 30% and 31%, respectively, and of stage 2 hypertension 41% and 43%, respectively. There was no statistical heterogeneity across the BP categories for the effects of liraglutide (P = .06 for MACE; P = .14 for nephropathy) or semaglutide (P = .40 for MACE; P = .27 for nephropathy) versus placebo. This implies that liraglutide and semaglutide may be beneficial for patients with type 2 diabetes, irrespective of their baseline BP.