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271.
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。 相似文献
272.
目的 观察利拉鲁肽对男性T2DM 合并骨质疏松（OP）患者的治疗作用。 方法 研究病例均选自2018至2019年在我科住院的 T2DM患者,其中合并骨质疏松患者（OP 组）68 例,不合并骨质疏松的患者60 例,分别就两组患者病程、年龄、糖化血红蛋白、血脂、骨代谢指标及 BMD 水平进行差异性比较;然后将OP 组患者就治疗前、治疗12周及停药12周的骨代谢、骨密度进行研究比较。结果 ①OP 组 BMI、HbA1c、TC、TG、LDL、PTH、OC、TP1NP、β-CTX较 T2DM 组升高,BMD 降低;②男性T2DM 合并骨质疏松患者应用利拉鲁肽12周后,其BMI、HbA1c、LDL、TG、TP1NP、β-CTX均降低,25-OH-D、BMD升高;利拉鲁肽停止使用12周即研究结束时,OP组患者的TP1NP、HbA1c较停药前有所上升,而BMD则呈下降趋势;③OP组治疗12周时与对照组比较,HbA1c无明显差异,但LDL、TP1NP水平下降,25羟维生素D、BMD则上升,OP组BMI值与T2DM组差异缩小,肥胖程度改善。结论 利拉鲁肽除了有其良好的降糖效果,同时对体重管控及调节血脂均有益处,而且可以提高骨密度,并且这种对骨质的改善作用是独立于血糖血脂控制带来的骨质改善作用之外的,对于2型糖尿病合并骨质疏松症的患者能够双效治疗,可作为糖尿病合并骨质疏松症患者首选推荐用药,既能改善血糖血脂、管理体重,还能增加骨密度。 相似文献
273.
Maurizio Rondinelli Antonio Rossi Alessandra Gandolfi Fabio Saponaro Loredana Bucciarelli Guido Adda Chiara Molinari Laura Montefusco Claudia Specchia Maria Chiara Rossi Marco Scardapane Maura Arosio Stefano Genovese 《Clinical therapeutics》2017,39(1):159-169
Purpose
An observational retrospective study was conducted by 2 diabetes clinics in Italy to assess patterns of use and long-term effectiveness of liraglutide on established and emerging parameters.Methods
Data from 261 patients with type 2 diabetes who started treatment with liraglutide between 2010 and 2014 were collected. Hierarchical linear regression models were applied to assess trends over time of clinical parameters. Factors associated with higher likelihood of dropout were identified through multivariate logistic analysis.Findings
Liraglutide was initiated as a switch in 42.5% of patients and as an add-on in 49.8%; in 7.7% of the patients initiation of liraglutide was associated with a reduction in the number of pharmacologic agents. A statistically significant reduction after 36 months was found for the following parameters (mean change [95% CIs]): glycosylated hemoglobin (HbA1c; –1.01% [1.34% to –0.68%]), fasting blood glucose (–27.5 [–40.6 to –14.4] mg/dL), weight (–2.9 [–4.5 to –1.3] kg), body mass index (–1.13 [–1.76 to –0.50] kg/m2), waist circumference (–1.74 [–3.85 to –0.37] cm), and LDL-C (–24.7 [–36.67 to –12.8] mg/dL). Improvements in systolic (–3.5 mm Hg) and diastolic (–2.3 mm Hg) blood pressures were observed at 24 months. Albuminuria was reduced by –16.6 mg/L during 36 months, although statistical significance was not reached. Glomerular filtration rate and heart rate were unchanged. Reductions in HbA1c between –0.6% and –1.3% were obtained in specific subgroups. Treatment was effective also in patients with >20 years of diabetes duration, although the likelihood of dropout was 6% higher for each additional year of disease duration (RR = 1.06; 95% CI, 1.01–1.12). The likelihood of dropout was almost four times higher for subjects treated with insulin (RR = 3.82; 95% CI, 1.22–11.96) and more than twice for those treated with sulfonylureas (RR = 2.39; 95% CI, 1.16–4.94) compared with patients not treated with these agents.Implications
Liraglutide used in routine clinical conditions maintains its effectiveness on metabolic control and weight after 3 years. Improvements in terms of metabolic control were found when liraglutide was used as both switch and add-on treatment. In addition, improvements were sustained when liraglutide replaced sulfonylureas or insulin. Diabetes duration had no impact on drug efficacy. Long-term benefits relative to blood pressure and LDL-C were also found, which could not be entirely explained by antihypertensive/lipid-lowering treatment intensification. No major effect on renal parameters was documented. Diabetes duration and some concomitant treatments were associated with a higher likelihood of liraglutide discontinuation. These data can contribute to improve appropriateness and cost-effectiveness profile of liraglutide. 相似文献274.
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277.
《Expert review of clinical pharmacology》2013,6(2):179-188
‘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. 相似文献
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279.
Ehtasham Ahmad MRCP Helen L. Waller PhD Jack A. Sargeant PhD M'Balu A. Webb PhD Zin Zin Htike PhD Gerry P. McCann MD Gaurav Gulsin PhD Kamlesh Khunti FMedSci Tom Yates PhD Joseph Henson PhD Melanie J. Davies MD David R. Webb PhD 《Diabetes, obesity & metabolism》2021,23(6):1409-1414
The mechanisms behind the beneficial cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared with dipeptidyl peptidase-4 inhibitors (DPP4is) remain largely unknown, despite both targeting the incretin pathway to improve glycaemic control. In these prespecified secondary analyses of the LYDIA trial, we examined the impact of the GLP-1RA liraglutide (1.8 mg once-daily) and the DPP4i sitagliptin (100 mg once-daily) on circulating cardiovascular biomarkers associated with atherosclerotic risk, including circulating progenitor cells (CPCs). LYDIA was a 26-week, randomized, active-comparator trial in 61 adults with type 2 diabetes and obesity (mean ± SD: age 43.8 ± 6.5 years, body mass index 35.3 ± 6.4 kg/m2, HbA1c 7.5% ± 0.83% [58.5 ± 9.1 mmol/mol]). Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1-alpha (SDF-1ɑ), both of which are implicated in endothelial function, were higher at 26 weeks with liraglutide therapy compared with sitagliptin (mean between-group difference [95% CI]: 77.03 [18.29, 135.77] pg/mL, p = .010; and 996.25 [818.85, 1173.64] pg/mL, p < .001, respectively). There were no between-group differences in CPCs, nitric oxide, C-reactive protein, interleukin-6, tumour necrosis factor alpha and advanced glycation end-products. These analyses suggest a favourable impact of liraglutide on VEGF and SDF-1ɑ levels compared with sitagliptin. These factors may therefore be implicated in the differential cardiovascular effects observed between these agents in large cardiovascular outcome trials. However, these are secondary analyses from a previous trial and thus hypothesis-generating. Purposive trials are required to examine these findings further. 相似文献