GLP-1受体激动剂：阿必鲁肽（albiglutide）治疗2型糖尿病疗效与安全性的系统评价

发布时间：2018-10-09 15:06

【摘要】：目的:运用系统评价方法建立阿必鲁肽(albiglutide)治疗2型糖尿病临床合理应用评价体系,为规范说明书用药提供循证医学证据。方法:电子检索中英文数据库EBSCO、PubMed(Medline)、OVID(包括Embase)、Cochrane library、中国知网(CNKI)、万方医学网(wanfang database)、维普中文期刊全文数据库(VIP)及中国生物医学全文数据库(CBM)中有关阿必鲁肽治疗2型糖尿病的临床随机对照试验(RCT),检索时限为2000年1月至2016年10月,并辅以手工检索相关杂志和网站。2名研究者按照纳入与排除标准,筛选文献、数据提取和交叉核对,并按文献质量评估标准予以文献偏倚风险评估。采用RevMan 5.0软件对各干预措施组中效应指标进行Meta分析及发表偏倚评估。结果:纳入10篇随机对照试验,文献偏倚风险均较低,其中8篇属于高质量研究,涉及有效2型糖尿病患者数2360例,其中阿必鲁肽组1199例,安慰剂组613例,阳性药西格列汀组548例。Meta分析结果显示:治疗周期末,(1)与安慰剂组患者相比,阿必鲁肽组患者糖化血红蛋白(HbA1c)水平(MD=-0.89,95%CI:-1.11~-0.66,P0.001)、空腹血浆葡萄糖(FPG)水平(MD=-1.58,95%CI:-1.90~-1.26,P0.001)、Hb A1c(7%)达标率(RR=3.01,95%CI:2.34~3.87,P0.001)、低血糖发生率(RR=1.64,95%CI:1.09~2.48,P0.05)和注射部位反应(ISR)发生率(RR=2.36,95%CI:1.61~3.47,P0.001)差异有统计学意义,hba1c、fpg水平低且波动范围不大,hba1c(7%)达标率高,但低血糖、isr发生率高,而因不良事件(ae)退出率、严重不良反应(sae)(致命或非致命)发生率和其他不良反应(腹泻、恶心、呕吐、便秘、消化不良、头痛、眩晕、背痛、腹痛、高血压、鼻咽炎、上呼吸道感染、泌尿道感染和表皮剥落型皮疹)发生率差异却无统计学意义(p0.05);(2)与阳性药西格列汀组患者相比,阿必鲁肽组患者hba1c水平(md=-0.36,95%ci:-0.47~-0.25,p0.001)、fpg水平(md=-1.06,95%ci:-1.35~-0.77,p0.001)、hba1c(7%)达标率(rr=1.40,95%ci:1.10~1.78,p0.05)、低血糖发生率(rr=1.55,95%ci:1.10~2.19,p0.05)和isr发生率(rr=2.56,95%ci:1.69~3.89,p0.001)差异有统计学意义,hba1c、fpg水平低且同样波动范围不大,hba1c(7%)达标率高,但低血糖、isr发生率也较高,而因ae退出率、sae(致命或非致命)发生率和其他不良反应(腹泻、恶心、高血压、鼻咽炎和上呼吸道感染)发生率差异却无统计学意义(p0.05)。结论:(1)就现有证据而言,阿必鲁肽对2型糖尿病患者的hba1c水平和fpg水平有良好的控制效果,hba1c(7%)达标率较为理想,常见胃肠道反应,如恶心、呕吐、腹泻、便秘和腹痛等症状患者均可耐受,未影响继续治疗,高血压、鼻咽炎、上呼吸道感染、泌尿道感染和表皮剥落型皮疹和sae发生率低,较为少见,但低血糖、isr与对照组相比发生率较高,可能会影响该药对患者的长期治疗。(2)因随机对照试验设计的局限性,如样本量、治疗周期、随访时间、受试患者个体差异及其他客观环境下的不确定等因素,均可影响试验结果,即也可能影响二次分析结果,因此,仍需大样本、高质量、严格设计的随机对照试验对阿必鲁肽进行长期的疗效与安全性研究加以验证。
[Abstract]:Objective: To establish an evaluation system for the clinical rational application of albilutide in the treatment of type 2 diabetes mellitus by using the system evaluation method. Methods: EBSCO, PubMed (Medline), OVID (including Embase), Cochrane Library, China Knowledge Network (CNKI) and Wanfang Medical Network (CNKI) were retrieved electronically. The clinical randomized controlled trial (RCT) of the full-text database (VIP) and Chinese Biomedical Full-text Database (CBM) for the treatment of type 2 diabetes mellitus (RCT) from January 2000 to October 2016, Related journals and websites were retrieved by hand, and 2 researchers conducted a literature bias risk assessment based on inclusion and exclusion criteria, screening literature, data extraction, and cross-checking, and by document quality assessment criteria. The effects of RevMan 5.0 software were analyzed and biased in each intervention group. Results: Among the 10 randomized controlled trials, the risk of literature bias was low, of which 8 were high-quality studies and 2360 patients with effective type 2 diabetes, including 1199 cases, 613 cases in the placebo group and 548 in the positive group. Meta-analysis showed that (1) Compared with the placebo group, the level of glycated hemoglobin (HbA1c) (MD =-0.89, 95% CI:-1.11 ~-0.066, P0.001), fasting plasma glucose (FPG) level (MD =-1.58, 95% CI:-1.90 ~-1.26, P0.001), Hb (7%) (RR = 3.01, 95% CI: 2.34 ~ 3.87, P0.001) were observed in patients with placebo group. The incidence of hypoglycemia (RR = 1.64, 95% CI: 1.09 ~ 2.48, P0.05) and injection site reaction (ISR) (RR = 2.36, 95% CI: 1.61 ~ 3.47, P0.001) had statistical significance, hba1c, fpg level was low and the fluctuation range was not large, hba1c (7%) was high, but the incidence of hypoglycaemia and isr was high. Serious adverse reactions (sae) (fatal or non-fatal) and other adverse reactions (diarrhea, nausea, vomiting, constipation, dyspepsia, headache, dizziness, back pain, abdominal pain, hypertension, rhinitis, upper respiratory tract infection, There was no significant difference in the incidence of infection and exfoliative rash (r = 0.05); (2) Compared with the patients who were positive, the level of hba1c (md =-0.036, 95% ci:-0.47 ~-0.025, p0.01), fpg level (md =-1.06, 95% ci:-1.35 ~-0.077, 100.0. 001), hba1c (7%) (r = 1. 40, 95% ci: 1. 10 ~ 1.78, p0.05). The incidence of hypoglycaemia (rr = 1. 55, 95% ci: 1. 10 ~ 2.19, 65.05) and isr (r = 2.56, 95% ci: 1.69 ~ 3.89, 01.001) were statistically significant, hba1c, fpg were low and the same wave range was not large, hba1c (7%) had a high incidence rate, but the incidence of hypoglycaemia and isr was also high, and the ae withdrawal rate was higher. The incidence of sae (fatal or non-fatal) and other adverse reactions (diarrhea, nausea, hypertension, nasal pharyngitis, and upper respiratory tract infection) was not statistically significant (P0.05). Conclusion: (1) As far as the existing evidence is concerned, Abiu peptide has good control effect on the hba1c level and fpg level of type 2 diabetes mellitus patients, hba1c (7%) is ideal, and the common gastrointestinal reactions such as nausea, vomiting, diarrhea, constipation and abdominal pain can be tolerated. No effect on the continuation of treatment, hypertension, rhinopharyngitis, upper respiratory tract infection, urinary tract infection and epidermal exfoliation type rash and sae incidence were low, but hypoglycemia, isr were higher in comparison with the control group, which could affect the long-term treatment of the drug for the patient. (2) Due to the limitations of randomized controlled trial design, such as sample size, treatment period, follow-up time, individual difference in subject trial and uncertain factors in other objective circumstances, the test results may be affected, i.e., the results of secondary analysis may also be affected, so large samples are still required. High-quality, strictly designed randomized controlled trials have been validated for the long-term efficacy and safety study of Abiropeptide.
【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1

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