利拉鲁肽对胰岛β细胞保护作用的研究进展

胰岛β细胞衰竭是糖尿病致病机制的核心,也是治疗2型糖尿病的关键靶点.已有众多基础及临床研究证实胰升糖素样肽1及其类似物利拉鲁肽具有葡萄糖依赖性降糖作用.同时,还具有显著改善胰岛β细胞功能的作用,为2型糖尿病的治疗提供了新的选择.     

Real-world clinical experience of Xultophy in the management of patients with type 2 diabetes in a secondary care clinic

Aims

Xultophy is the first fixed co-formulation pen containing insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, authorized for type 2 diabetes patients since 2014. The aim was to review the clinical effectiveness of Xultophy across two hospitals in Wales.

Glucagon‐like peptide‐1 analog liraglutide in combination with sulfonylurea safely improves blood glucose measures vs sulfonylurea monotherapy in Japanese patients with type 2 diabetes: Results of a 52‐week,randomized, multicenter trial

Aims/Introduction:  Sulfonylurea (SU) agents are the most effective drugs at lowering blood glucose when used alone. However, their effectiveness declines after a certain period. The addition of liraglutide to existing SU therapy might reverse some of the known drawbacks of SU.Materials and Methods:  This multicenter, randomized, 52‐week study assessed the long‐term efficacy and safety of adding liraglutide at 0.6 or 0.9 mg/day to existing SU therapy in Japanese patients with inadequately controlled type 2 diabetes.Results:  In total, 264 patients were enrolled and received treatment. At week 52, HbA_1c in the liraglutide 0.6 mg, liraglutide 0.9 mg and placebo groups was reduced from 9.00 to 7.91%, from 8.61 to 7.33%, and from 8.85 to 8.79%, respectively. The mean difference of HbA_1c (95% CI) in the liraglutide 0.6 and 0.9 mg groups vs the placebo group was 0.96 (−1.25 to −0.67) and −1.33 (−1.62 to −1.04), respectively. For the liraglutide 0.6 mg, 0.9 mg and placebo groups, the Japanese Diabetes Society target HbA_1c of <6.9% was achieved by 15.1, 39.1 and 4.5% of patients, respectively. Mean fasting plasma glucose at week 52 was lower in the liraglutide groups compared with the placebo group, and mean bodyweight remained unchanged in the liraglutide groups. Most subjects in all three treatment groups reported mild adverse events. No major hypoglycemic episode was reported.Conclusions:  Once‐daily administration of liraglutide in combination with SU for 52 weeks provided favorable metabolic control, a safety profile and did not alter bodyweight. This trial was registered with ClinicalTrial.gov (no. {"type":"clinical-trial","attrs":{"text":"NCT00395746","term_id":"NCT00395746"}}NCT00395746). (J Diabetes Invest,doi: 10.1111/j.2040‐1124.2011.00103.x, 2011)     

利拉鲁肽在人骨髓间充质干细胞诱导分化为胰岛素分泌细胞中的作用

目的 观察利拉鲁肽在入骨髓间充质干细胞( hBM-MSCs)向胰岛素分泌细胞(IPCs)方向分化诱导中的作用.方法 采用高糖、尼克酰胺和利拉鲁肽3阶段诱导方案对hBM-MSCs进行定向诱导分化,倒置显微镜下观察诱导过程中细胞的形态学变化,双硫腙染色法鉴定诱导后细胞,Western印迹法检测细胞胰腺十二指肠同源盒基因1( PDX-1)、葡萄糖转运蛋白2(GLUT2)、葡萄糖激酶(GK)、胰岛素的蛋白表达,ELISA检测细胞的胰岛素分泌水平.结果 添加10 nmol/L利拉鲁肽作用7d后诱导效率明显增加.诱导过程中细胞形态由长梭形逐渐变为圆形,并聚集生长,至诱导末出现大量圆形葡萄状聚集生长的胰岛样细胞团;双硫腙染色阳性细胞量、细胞PDX-1、GLUT2、GK、胰岛素的蛋白表达、细胞的基础和葡萄糖刺激的胰岛素分泌水平均逐渐增加(均P＜0.05).结论 在体外,高糖、尼克酰胺联合利拉鲁肽可使hBM -MSCs定向诱导分化为IPCs.     

Effects of GLP-1 receptor agonists on myokine levels and pro-inflammatory cytokines in patients with type 2 diabetes mellitus

Background and aimsTo evaluate the change in circulating serum irisin and interleukin-6 (IL-6), in patients with type 2 diabetes mellitus (T2DM) after 6 and 12 months of GLP-1 treatment.Methods and resultsEighty-five patients with T2DM inadequately controlled with insulin or other hypoglycaemic drugs were added to dulaglutide (N° = 44) and liraglutide (N° = 41) treatment.After 6 months of GLP-1 analogues a significant decrease in BMI (p < 0.001), waist circumference (WC) (p < 0.001), fasting blood glucose (p < 0.001), HbA1c (p < 0.001), total cholesterol (p < 0.001), LDL-cholesterol (p = 0.003), triglycerides (p = 0.017), IL-6 (p = 0.045) and a significant increase in serum irisin (p < 0.001) were observed compared to baseline. After 12 months of treatment no significant differences were found compared to the levels at 6 months. The change in irisin from baseline (Δ_irisin) was significantly related to the changes in total-cholesterol (Δ_total-cholesterol) (r = −0.293; p = 0.020), while the change in IL-6 (Δ_IL-6) was significantly related to the changes in WC (Δ_WC) (r = 0.347; p = 0.006).ConclusionsAdditive treatment with GLP1-analogues results in an increase in serum circulating irisin levels and a decrease in IL-6. The post-treatment change in irisin was correlated with a decrease in total cholesterol, while the change in IL-6 was correlated with a decrease in WC.     

利拉鲁肽与达格列净联合治疗2型糖尿病肾病的临床疗效分析

目的分析利拉鲁肽与达格列净联合治疗2型糖尿病肾病的临床疗效。方法回顾分析该院2019年2月—2020年4月期间收治的2型糖尿病肾病患者80例,按治疗方式分组,其中40例接受利拉鲁肽治疗(对照组),另40例接受达格列净联合利拉鲁肽治疗(观察组),比较治疗效果,即疗效、血糖指标、24 h尿总蛋白、24 h尿微量白蛋白、胱抑素C等指标。结果观察组疗效95.00%高于对照组67.50%,差异有统计学意义(P<0.05);比较血糖指标,治疗前组间数据差异无统计学意义(P>0.05),治疗后,观察组糖化血红蛋白、餐后2 h血糖、空腹血糖低于对照组,差异有统计学意义(P<0.05);比较24 h尿总蛋白、24 h尿微量白蛋白、尿微量白蛋白/尿肌酐(ACR)、胱抑素C、同型半胱氨酸,治疗前组间数据差异无统计学意义(P>0.05),治疗后,观察组24 h尿总蛋白、24 h尿微量白蛋白、尿微量白蛋白/尿肌酐(ACR)、胱抑素C、同型半胱氨酸均低于对照组,差异有统计学意义(P<0.05)。结论达格列净联合利拉鲁肽治疗2型糖尿病肾病,可更好地控制患者血糖指标,降低尿蛋白,疗效比单一使用利拉鲁肽治疗更理想。     

达格列净、利拉鲁肽对超重或肥胖2型糖尿病合并冠心病患者的糖脂代谢的影响

目的探讨达格列净、利拉鲁肽对超重或肥胖2型糖尿病合并冠心病患者的糖脂代谢的影响。方法随机纳入2018年6月—2020年1月该院就诊的160例超重或肥胖2型糖尿病合并冠心病患者为研究对象,分两组,每组80例。所有患者均口服盐酸二甲双胍片(格华止)≥1500 mg/d,达格列净组启始予5 mg,根据血糖情况调整药物剂量,如空腹血糖>7.0 mmol/L,则达格列净加量至10 mg,1次/d。利拉鲁肽组起始予0.6 mg,当空腹血糖>7.0 mmol/L,则利拉鲁肽加量至1.2 mg。对比两组患者治疗前和治疗12周后的HbA1c,空腹血糖、餐后2 h血糖、胰岛功能、体重指数和不良反应等。结果从改善糖代谢角度,两组患者空腹血糖、餐后血糖和糖化血红蛋白等比较差异无统计学意义(P>0.05),但达格列净组的体重指数改善较利拉鲁肽组明显,差异有统计学意义(P<0.05)。从改善胰岛功能角度,治疗12周后,利拉鲁肽组的胰岛素抵抗指数明显低于达格列净,差异有统计学意义(P<0.05);从安全角度,两组患者低血糖等不良反应发生率差异无统计学意义(P>0.05)。结论两种药物治疗肥胖型2型糖尿病合并冠心病的效果相当,但在改善胰岛素抵抗,利拉鲁肽具有更明显的优势。     

利拉鲁肽治疗2型糖尿病合并多囊卵巢综合征的临床价值研究

目的探讨利拉鲁肽治疗2型糖尿病合并多囊卵巢综合征的临床效果。方法选择2018年1月—2019年6月收治的2型糖尿病合并多囊卵巢综合征患者60例为对象,随机数表法将其分成对照组(n=30)和观察组(n=30)。对照组用二甲双胍治疗,观察组用二甲双胍联合利拉鲁肽治疗,治疗当天和治疗24周时,检测两组患者体内空腹血糖(FPG)、餐后2血糖(2 hPG)和糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)与促卵泡生成素(FSH)及黄体生成素(LH),比较两组患者用药后的不良反应发生率。结果治疗后两组的FPG、2 hPG与HbA1c、HOMA-IR及FSH、LH低于治疗前,观察组的FPG、2 hPG与HbA1c、HOMA-IR与FSH、LH低于对照组,差异有统计学意义(P<0.05)。两组用药后的不良反应发生率比较,差异无统计学意义(P>0.05)。结论2型糖尿病合并多囊卵巢综合征患者在用二甲双胍治疗时,联合利拉鲁肽治疗的效果更显著,可明显降低血糖水平和胰岛素抵抗指数,促使患者体内的性激素水平得到改善,不良反应少,用药安全性高。     

达格列净联合利拉鲁肽治疗非酒精性脂肪性肝病合并2型糖尿病患者短期疗效研究*

目的 探讨应用达格列净联合利拉鲁肽治疗非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2MD)患者的短期疗效。方法 2017年9月～2020年10月我院收治的60例NAFLD合并T2MD患者,采用随机数字表法将其分为观察组30例和对照组,均常规接受生活方式干预和二甲双胍口服控制血糖,在此基础上给予对照组利拉鲁肽治疗,观察组在对照组治疗的基础上给予达格列净口服,两组均持续治疗观察3个月。常规检测空腹血糖(FPG)、餐后2 h血糖 (2h PG)、糖化血红蛋白 (HbA1c)及甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇 (LDL－C ) 和高密度脂蛋白胆固醇 (HDL－C)水平;使用自动免疫分析仪检测空腹胰岛素(Fins)和餐后2 h胰岛素(2hIns)水平,计算胰岛素抵抗指数(HOMA-IR);使用Fibrotouch检测肝脏脂肪受控衰减参数(CAP)。结果 在治疗3个月末,观察FPG、2hPG和HbA1水平分别为(5.8±0.7)mmol/L、(6.9±0.8)mmol/L和(6.3±0.9)%,显著低于对照组【分别为(6.6±0.6)mmol/L、(7.7±0.7)mmol/L和(7.2±1.0)%,P＜0.05】;观察组血清Fins、2hIns和HOMA-IR水平分别为(9.8±1.2)mIU/L、(20.2±1.7)mIU/L和(2.6±0.4)%,显著低于对照组【分别为(11.9±1.1)mmol/L、(24.8±1.6)mmol/L和(3.2±0.5)%,P＜0.05】;观察组血清TG水平为(2.6±0.4) mmol/L,显著低于对照组【(3.0±0.3)mmol/L,P＜0.05】,血清HDL-C水平为(1.6±0.2) mmol/L,显著高于对照组【(1.2±0.3)mmol/L,P＜0.05】,CAP为(249.2±7.5)dB/m,显著低于对照组【(264.7±8.6)dB/m,P＜0.05】;观察组血清AST水平为(39.9±3.8)U/L,显著低于对照组【(44.9±4.2)U/L,P＜0.05】。结论 应用达格列净联合利拉鲁肽治疗NAFLD合并T2MD患者可取得短期疗效,帮助有效控制血糖和血脂水平,减轻胰岛素抵抗,改善肝功能,显示出良好的疾病治疗前景。     

人GLP-1类似物利拉鲁肽的最新研究进展

研究证实,新型胰升糖素样肽-1(GLP-1)类似物可以解决糖尿病治疗中存在的多种问题,因而受到各国学者的广泛关注.本文概括了GLP-1的生理作用和长效人GLP-1类似物利拉鲁肽的延长作用机制,同时重点介绍了利拉鲁肽的最新基础与临床研究进展.