Variability in estimated glomerular filtration rate and the risk of major clinical outcomes in diabetes: Post hoc analysis from the ADVANCE trial

There are limited data on whether estimated glomerular filtration rate (eGFR) variability modifies the risk of future clinical outcomes in type 2 diabetes (T2D). We assessed the association between 20-month eGFR variability and the risk of major clinical outcomes in T2D among 8241 participants in the ADVANCE trial. Variability in eGFR (coefficient of variation [CV_eGFR]) was calculated from three serum creatinine measurements over 20 months. Participants were classified into three groups by thirds of CV_eGFR: low (≤6.4; reference), moderate (>6.4 to ≤12.1) and high (>12.1). The primary outcome was the composite of major macrovascular events, new or worsening nephropathy and all-cause mortality. Cox regression models were used to estimate hazard ratios (HRs). Over a median follow-up of 2.9 years following the 20-month period, 932 (11.3%) primary outcomes were recorded. Compared with low variability, greater 20-month eGFR variability was independently associated with higher risk of the primary outcome (HR for moderate and high variability: 1.07, 95% CI: 0.91–1.27 and 1.22, 95% CI: 1.03–1.45, respectively) with evidence of a positive linear trend (p = .015). These data indicate that eGFR variability predict changes in the risk of major clinical outcomes in T2D.     

Effect of once-weekly dulaglutide versus insulin glargine in people with type 2 diabetes and different baseline glycaemic patterns: A post hoc analysis of the AWARD-2 clinical trial

The long-acting glucagon-like peptide-1 receptor agonist dulaglutide acts by stimulating insulin secretion and reducing glucagon levels in a glucose-dependent manner both in the fasting and postprandial states, resulting in reductions of both fasting glucose (FG) and postprandial glucose (PPG). In contrast, the main mechanism of action of basal insulin is to reduce elevated FG by inhibiting hepatic glucose production. The aim of the present post hoc analysis of the phase 3 AWARD-2 trial was to investigate whether specific baseline glycaemic patterns respond differentially to dulaglutide compared to insulin glargine (glargine). We categorized participants into four subgroups based on prespecified glucose thresholds and their baseline FG and daily 2-hour mean PPG: low FG/low PPG; low FG/high PPG; high FG/low PPG; and high FG/high PPG. Changes in glycaemic measures in response to treatment with dulaglutide or glargine were evaluated in each subgroup. At 52 weeks, significant reductions from baseline in glycated haemoglobin (HbA1c) were observed in all subgroups with dulaglutide 1.5 mg and with glargine (all P < .05), except in patients with low FG/low PPG who received glargine. Greater HbA1c reductions were observed with dulaglutide 1.5 mg compared to glargine in all subgroups (all P ≤ .05), except in the low FG/high PPG subgroup.     

Achievement of glycaemic control is associated with improvements in lipid profile with iGlarLixi versus iGlar: A post hoc analysis of the LixiLan-L trial

Diabetic dyslipidaemia is a major risk factor for accelerated atherosclerosis. Glycaemic treatments that improve dyslipidaemia may help reduce the burden of atherosclerosis. This analysis investigated the effect of iGlarLixi [insulin glargine U100 (iGlar) and lixisenatide] versus iGlar on lipid profiles in patients with type 2 diabetes uncontrolled on basal insulin. Data from LixiLan-L were used to estimate changes in fasting lipid levels from baseline to week 30, overall and in patients stratified by achievement of glycaemic targets {2-hour postprandial glucose [≤10, >10 mmoL/L], fasting plasma glucose [≤6.1, >6.1 mmoL/L], HbA1c [≤7, >7% (≤53, >53 mmol/mol)]}. At week 30, median percentage change in triglycerides remained nearly unchanged (0.3% increase) with iGlarLixi versus a 6.5% increase with iGlar (P = 0.035; overall); similarly, trends towards better total and LDL cholesterol levels were observed with iGlarLixi versus iGlar. In patient subgroups achieving glycaemic targets, all lipid variables except for HDL cholesterol improved with iGlarLixi but not with iGlar. In summary, patients with type 2 diabetes uncontrolled on basal insulin showed improved fasting lipid profiles with iGlarLixi compared with iGlar, particularly when achieving glycaemic targets.     

Cardiovascular and mortality outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: A meta-analysis with the FREEDOM cardiovascular outcomes trial

Background and aimsFREEDOM, a cardiovascular outcome trial with a GLP-1 receptor agonist, testing a continuous subcutaneous infusion of exenatide (ITCA 650), recently reported its findings.MethodsWe meta-analysed its results with eight prior GLP-1 receptor agonists trials.ResultsGLP-1 receptor agonists reduced MACE by 13% (HR 0.87 [95% CI 0.81–0.94]; p = 0.00065) and all-cause mortality by 11% (HR 0.89 [0.83–0.95]; p = 0.00084). However, FREEDOM results appear dissimilar to prior GLP-1 receptor agonist trials.ConclusionFREEDOM results should not influence current considerations about the benefits or harms of approved formulations of GLP-1 receptor agonists. There is also an ongoing debate about the safety of ITCA 650.     

不同公式计算的估算肾小球滤过率对老年慢性肾脏病预后的分析

目的对比不同慢性肾脏病流行病合作研究(CKD-EPI)公式计算的估算肾小球滤过率(eGFR)在评估老年慢性肾脏病(CKD)患者预后中的诊断价值,并分析影响终点事件的危险因素。方法选取2015年3月至2018年12月于北京友谊医院医疗保健中心行健康体检的具有4年连续资料的老年人共682例。采用基于肌酐(Cr)的CKD-EPI(CKD-EPI_(Cr))公式、基于胱抑素C(Cys)的CKD-EPI(CKD-EPI_(Cys))公式及基于Cr和Cys联合的CKD-EPI(CKD-EPI_(CrCys))公式分别计算eGFR,评估各公式计算的eGFR对终点事件(全因死亡、心血管事件、急性肾损伤、快速肾功能下降)的诊断价值,分析影响预后的危险因素。采用SPSS 23.0软件进行数据处理。依据数据类型,组间比较分别采用t检验或χ~2检验。受试者工作特征(ROC)曲线评估诊断价值,logistic回归分析影响预后的危险因素。结果 CKD-EPI_(Cys)(AUC=0.692,P0.001)及CKD-EPI_(CrCys)(AUC=0.647,P0.001)公式计算的eGFR对终点事件有诊断价值,其中CKD-EPI_(Cys)公式的诊断价值较高。CKD-EPI_(Cys)与CKD-EPI_(CrCys)公式计算eGFR评估的终点事件的危险因素相同,均为尿白蛋白/肌酐比值(UACR)(OR=2.263,95%CI 1.359～3.771)、高血压(OR=1.679,95%CI 1.143～2.467)、贫血(OR=1.959,95%CI 1.245～3.084)及住院次数(OR=1.471,95%CI 1.321～1.637)。结论 CKD-EPI_(Cys)公式计算的eGFR对老年CKD预后评估的诊断价值最有优势。UACR、贫血、高血压和住院次数是老年CKD患者发生终点事件的独立危险因素。     

改善心血管和肾脏结局的新型抗高血糖药物临床应用中国专家建议

动脉粥样硬化性心血管病(ASCVD)和(或)慢性肾脏病(CKD)不但是2型糖尿病(T2DM)常见合并疾病,也是T2DM患者致残和致死的首要原因。近年来一系列临床研究证据表明,新型抗高血糖药物胰高糖素样肽-1受体激动剂(GLP-1 RA)和钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)类药物能显著改善心血管和肾脏结局的临床获益,且安全性良好。为促使T2DM的治疗模式从单纯控制血糖转移到改善心血管和肾脏临床结局,中国心血管病学、内分泌学、肾脏病学和神经病学专家组成的专家组梳理了GLP-1 RA或SGLT2i的心血管保护的临床证据、可能机制和常见不良反应,提出了对这两类药物在临床实践中的合理定位、应用建议和注意事项,鼓励临床医师在临床实践中对T2DM患者及早启动并长期维持能够改善心血管和肾脏结局的新型抗高血糖药物治疗。