Diagnostic and Therapeutic Uses of Intestinal Intubation

Intubation of the intestine is widely employed in the clinical management of patients. In this article are discussed some of the more important applications of this procedure in the diagnosis and treatment of intestinal, biliary and pancreatic diseases.     

胰岛素泵与利拉鲁肽治疗老年超重2型糖尿病的疗效与安全性

目的:探讨胰岛素泵与利拉鲁肽治疗在老年超重2型糖尿病患者中的应用效果。方法:将68例老年超重2型糖尿病患者分为观察组(胰岛素泵)和对照组(利拉鲁肽)各34例,对比其治疗效果。结果:与对照组相比,观察组患者的治疗有效率(94.12%>73.53%)、SF-36评分((78.82±4.24)分>(69.14±5.16)分)相对更高(P<0.05),并发症发生率(8.82%<32.35%)、FBG((6.29±1.05)<(8.04±1.16)mmol/L)、2h PBG((8.74±1.38)<(10.39±1.57)mmol/L)、BMI((23.51±2.04)<(27.75±2.36)kg/m²)相对更低(P<0.05)。结论:老年超重2型糖尿病的临床治疗,胰岛素泵治疗在疗效和安全性方面具有显著优势。     

A randomized controlled trial protocol of the cardiovascular safety and efficacy of liraglutide in the treatment of type 2 diabetes

Background:Recently, many clinical experiments have evaluated the influences of liraglutide in the treatment of type 2 diabetes. However, the outcomes of these studies are inconsistent, and the number of high-quality prospective trials that conducted to assess the cardiovascular safety is limited. Hence, for this research, it was implemented for the assessment of the cardiovascular effectiveness and safety of liraglutide in type 2 diabetes patients.Methods:This research was a 26-week active controlled and randomized trial. Our research protocol follows the guidelines of Good Clinical Practice issued via the Helsinki Declaration and International Conference on Coordination. All the patients will receive the written informed consent in order to involve in our clinical experiment. The participants with type 2 diabetes aged from 18 years to 80 years, patients with 45.0 kg/m² body-mass index or less, and with glycosylated hemoglobin of 7.5 to 10.0 percent, and received metformin (daily 1500 mg or more) for 3 months or longer were eligible. All the patients were randomized to 1 of 2 interventions (in the ratio of 1:1): liraglutide placebo once daily (blinded) and liraglutide once daily (blinded), respectively, both combined with the glimepiride and metformin (open-labeled). For the efficacy variable, the major endpoint was the baseline glycated hemoglobin change after treating for 26 weeks. The secondary end points involved: the percentage of participants who achieved the goals of postprandial blood glucose, fasting blood glucose, and glycosylated hemoglobin; the changes of mean postprandial blood glucose, fasting blood glucose, and the body weight, pancreatic B-cell function index, and changes in blood pressure and insulin resistance assessed by homeostasis model.Conclusions:For this research, the limitations involve the short trial period and the limitation of glimepiride in some countries, thus excluding the maximum doses of glimepiride.Trial registration:This study protocol was registered in Research Registry (researchregistry6306).     

利拉鲁肽对人HepG2肝细胞脂代谢的影响及作用机制

目的:建立HepG2肝细胞脂肪变性模型,了解利拉鲁肽是否可改善HepG2细胞内脂代谢状态,并对相关机制进行初步探讨?方法:软脂酸钠诱导建立HepG2肝细胞脂肪变性模型,并给予利拉鲁肽干预?油红O染色确定HepG2肝细胞脂肪变性模型的建立?Western blot检测HepG2 中脂质合成和分解关键酶蛋白水平的变化情况及HepG2 中PI3K信号通路活化情况?采用PI3K信号通路抑制剂预处理HepG2 细胞,观察PI3K信号通路在软脂酸钠诱导建立HepG2肝细胞脂肪变性中的作用?结果:油红O染色结果显示模型建立成功?Western blot结果显示,软脂酸钠诱导可显著升高HepG2中固醇调节元件结合蛋白1c(sterol regulatory element-binding protein1c,SREBP1c)?脂肪酸合成酶(fatty acid synthase,FAS)的蛋白水平,降低脂肪甘油三酯脂酶(adipose triglyceride lipase,ATGL)的蛋白水平(P < 0.01),并上调HepG2中PI3K信号通路活化水平;与软脂酸钠组相比,利拉鲁肽干预可显著降低HepG2中SREBP1c?FAS 的蛋白水平,升高ATGL的蛋白水平,并抑制HepG2中PI3K信号通路活化水平;阻断HepG2中的PI3K信号通路后,软脂酸钠诱导HepG2脂肪变性的能力显著降低(P < 0.01)?结论:利拉鲁肽可通过调节HepG2中的PI3K信号通路,进而改善HepG2细胞的脂代谢情况?     

Liraglutide,a once‐daily human GLP‐1 analogue,improves pancreatic B‐cell function and arginine‐stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus

Aims To assess the effect of liraglutide, a once‐daily human glucagon‐like peptide‐1 analogue on pancreatic B‐cell function. Methods Patients with Type 2 diabetes (n = 39) were randomized to treatment with 0.65, 1.25 or 1.9 mg/day liraglutide or placebo for 14 weeks. First‐ and second‐phase insulin release were measured by means of the insulin‐modified frequently sampled intravenous glucose tolerance test. Arginine‐stimulated insulin secretion was measured during a hyperglycaemic clamp (20 mmol/l). Glucose effectiveness and insulin sensitivity were estimated by means of the insulin‐modified frequently sampled intravenous glucose tolerance test. Results The two highest doses of liraglutide (1.25 and 1.9 mg/day) significantly increased first‐phase insulin secretion by 118 and 103%, respectively (P < 0.05). Second‐phase insulin secretion was significantly increased only in the 1.25 mg/day group vs. placebo. Arginine‐stimulated insulin secretion increased significantly at the two highest dose levels vs. placebo by 114 and 94%, respectively (P < 0.05). There was no significant treatment effect on glucose effectiveness or insulin sensitivity. Conclusions Fourteen weeks of treatment with liraglutide showed improvements in first‐ and second‐phase insulin secretion, together with improvements in arginine‐stimulated insulin secretion during hyperglycaemia.     

Achieving a clinically relevant composite outcome of an HbA1c of <7% without weight gain or hypoglycaemia in type 2 diabetes: a meta-analysis of the liraglutide clinical trial programme

Aim: Effective type 2 diabetes management requires a multifactorial approach extending beyond glycaemic control. Clinical practice guidelines suggest targets for HbA1c, blood pressure and lipids, and emphasize weight reduction and avoiding hypoglycaemia. The phase 3 clinical trial programme for liraglutide, a human glucagon‐like peptide 1 analogue, showed significant improvements in HbA1c and weight with a low risk of hypoglycaemia compared to other diabetes therapies. In this context, we performed a meta‐analysis of data from these trials evaluating the proportion of patients achieving a clinically relevant composite measure of diabetes control consisting of an HbA1c <7% without weight gain or hypoglycaemia. Methods: A prespecified meta‐analysis was performed on 26‐week patient‐level data from seven trials (N = 4625) evaluating liraglutide with commonly used therapies for type 2 diabetes: glimepiride, rosiglitazone, glargine, exenatide, sitagliptin or placebo, adjusting for baseline HbA1c and weight, for a composite outcome of HbA1c <7.0%, no weight gain and no hypoglycaemic events. Results: At 26 weeks, 40% of the liraglutide 1.8 mg group, 32% of the liraglutide 1.2 mg group and 6–25% of comparators (6% rosiglitazone, 8% glimepiride, 15% glargine, 25% exenatide, 11% sitagliptin, 8% placebo) achieved this composite outcome. Odds ratios favoured liraglutide 1.8 mg by 2.0‐ to 10.5‐fold over comparators. Conclusions: As assessed by the composite outcome of HbA1c <7%, no hypoglycaemia and no weight gain, liraglutide was clearly superior to the other commonly used therapies. However, the long‐term clinical impact of this observation remains to be shown.     

Liraglutide improves obesity-induced renal injury by alleviating uncoupling of the glomerular VEGF–NO axis in obese mice

Obesity-related kidney disease is associated with generalized endothelial dysfunction. Liraglutide, a glucagon-like peptide-1 agonist, has cardiovascular–renal protective effects in patients with diabetes. In this study, the ability of liraglutide to reduce urinary albumin excretion by alleviating glomerular vascular endothelial growth factor-nitric oxide (VEGF–NO) axis uncoupling was assessed in high fat diet-induced obese mice. C57BL/6J mice were divided into control and obesity groups, treated with or without liraglutide (200 μg/kg/day). Blood biochemistry and urinary albumin excretion were measured. Glomerular VEGF and the AMPK–endothelial nitric oxide synthase (eNOS) pathway were assayed by western blotting. Glomerular NO, renal haeme oxygenase-1 activity, and malondialdehyde levels were also measured. Treatment of obese mice with liraglutide led to significant reductions in body weight gain (46 ± 1 g vs 55 ± 1 g, P < .0001), visceral fat (8.9 ± 0.6 g vs 14.5 ± 0.6 g, P < .0001), perirenal fat (2.9 ± 0.2 g vs 5.4 ± 0.3 g, P < .0001), and free fatty acid (1.71 ± 0.12 mmol/L vs 1.02 ± 0.08 mmol/L, P < .0001). Liraglutide significantly improved glucose homeostasis, which was impaired in obese mice. Liraglutide reduced urinary albumin excretion and glomerular hypertrophy in obese mice. Additionally, liraglutide significantly decreased VEGF and increased glomerular NO production in glomeruli, indicating restoration of the glomerular VEGF–NO axis. Furthermore, liraglutide activated the glomerular AMPK–eNOS pathway in obese mice, upregulated renal haeme oxygenase-1 activity, and reduced the renal malondialdehyde levels in obese mice. In conclusion, liraglutide reduced microalbuminuria and ameliorated renal injury by alleviating the uncoupling of the glomerular VEGF–NO axis.     

Usability of the Novel Liraglutide 3.0 mg Pen Injector Among Overweight or Obese Adult Patients With or Without Prior Injection Experience

Background:

Obesity is associated with multiple comorbidities and increased mortality, making it an important target for treatment. However, achieving and maintaining weight loss by diet and physical activity remains challenging, and may often require pharmacotherapy. Liraglutide 3.0 mg has recently been approved for weight management in the United States, Canada, and EU. The current analysis used a summative usability test to assess safety and effectiveness, ease of use, and training requirements for the novel liraglutide 3.0 mg pen injector.

Methods:

Of the 234 participants, half received instructions for use and video-based training and/or opportunity to handle the device. All participants (excluding pharmacists) performed 6 tasks followed by post- task interviews on task difficulty, device ease of use, and any use errors, close calls, and operational difficulties. Tasks included differentiation of correct box and pen injector, medication clarity assessment, normal, dose reversal, and end-of-content injection. Number/type of use errors, close calls, and operational difficulties were evaluated.

Results:

All assessed participants interpreted the instructions for use correctly. No potentially serious use errors, and low numbers of nonserious errors, were reported. Overall, participants committed 105 use errors related to handling, with no potential for harm. A total of 25 close calls and 44 operational difficulties were reported without any pattern indicative of a design flaw. Marked differences in the incidence of events were observed for trained versus untrained participants regardless of prior injection experience. Participants rated ease of use as 6.4/7.

Conclusions:

The liraglutide 3.0 mg pen injector is safe and easy to use for liraglutide administration. New device features allow for safe use after brief training.