度拉糖肽每周一次给药用于2型糖尿病合并2/3期慢性肾脏病患者的安全性和有效性
Safety and Efficacy of Exenatide Once Weekly in Participants with Type 2 Diabetes and Stage 2/3 Chronic Kidney Disease.
作者信息
Guja Cristian, Frías Juan P, Suchower Lisa, Hardy Elise, Marr Galina, Sjöström C David, Jabbour Serge A
机构信息
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
National Research Institute, Los Angeles, CA, USA.
出版信息
Diabetes Ther. 2020 Jul;11(7):1467-1480. doi: 10.1007/s13300-020-00815-z. Epub 2020 Apr 18.
INTRODUCTION
The safety and efficacy of exenatide once weekly (EQW) is overall well established. EQW is primarily renally eliminated. In this study, the efficacy and renal and gastrointestinal tolerability of EQW were summarised in participants with type 2 diabetes and chronic kidney disease stage 3 (CKD3; moderate renal impairment; estimated glomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min/1.73 m) or CKD stage 2 (CKD2; mild renal impairment; eGFR ≥ 60 to < 90 mL/min/1.73 m).
METHODS
Data on participants with type 2 diabetes and baseline CKD3 or CKD2 from eight phase 3, double-blind or open-label studies with 26- or 28-week controlled treatment periods were pooled. Participants received EQW or a placebo/non-glucagon-like peptide-1 receptor agonist comparator (sitagliptin, metformin, pioglitazone, dapagliflozin and insulin).
RESULTS
Participants with baseline CKD3 (N = 182) or CKD2 (N = 772) receiving EQW differed in a number of baseline characteristics, such as age < 65 years, race, mean body mass index and mean type 2 diabetes duration, whereas mean blood pressure and glycated haemoglobin (HbA) were similar. Mean reductions in HbA, body weight and systolic blood pressure from baseline to week 26/28 in participants receiving EQW were similar between the CKD subgroups. The proportions of participants (CKD3 and CKD2) with any adverse event (AE) were 81% and 72%, respectively, for EQW and 74% and 68%, respectively, for all comparators; those for serious AEs were 2.7% and 3.4%, respectively, for EQW and 6% and 5%, respectively, for all comparators. Gastrointestinal AE rates were higher in the EQW CKD3 subgroup (42.2% of participants) than in the CKD2 (32.8%) subgroup, although rates for nausea and vomiting were similar. There were no dehydration events; one participant in each treatment group had a serious AE of acute kidney injury (EQW with CKD3, n = 1; pioglitazone with CKD2, n = 1).
CONCLUSION
Exenatide once weekly was well tolerated and demonstrated similar efficacy in participants with type 2 diabetes with mild and moderate renal impairment.
TRIAL REGISTRATION
ClinicalTrials.gov identifiers: NCT00637273, NCT00676338, NCT02229383, NCT02229396, NCT00641056, NCT01652729, NCT00935532, NCT01003184.
引言
艾塞那肽每周一次（EQW）的安全性和有效性总体上已得到充分证实。EQW主要通过肾脏清除。在本研究中，总结了2型糖尿病合并慢性肾脏病3期（CKD3；中度肾功能损害；估计肾小球滤过率[eGFR]≥30至<60 mL/min/1.73 m²）或CKD2期（CKD2；轻度肾功能损害；eGFR≥60至<90 mL/min/1.73 m²）患者中EQW的疗效、肾脏和胃肠道耐受性。
方法
汇总了八项3期双盲或开放标签研究中2型糖尿病且基线为CKD3或CKD2的参与者的数据，这些研究的对照治疗期为26或28周。参与者接受EQW或安慰剂/非胰高血糖素样肽-1受体激动剂对照药物（西他列汀、二甲双胍、吡格列酮、达格列净和胰岛素）。
结果
接受EQW的基线为CKD3（N = 182）或CKD2（N = 772）的参与者在一些基线特征方面存在差异，如年龄<65岁、种族、平均体重指数和2型糖尿病平均病程，而平均血压和糖化血红蛋白（HbA）相似。在接受EQW的参与者中，从基线到第26/28周，CKD亚组间HbA、体重和收缩压的平均降低相似。EQW组（CKD3和CKD2）发生任何不良事件（AE）的参与者比例分别为81%和72%，所有对照药物组分别为74%和68%；严重AE的比例，EQW组分别为2.7%和3.4%，所有对照药物组分别为6%和5%。EQW的CKD3亚组胃肠道AE发生率（42.2%的参与者）高于CKD2亚组（32.8%），尽管恶心和呕吐发生率相似。没有脱水事件；每个治疗组各有一名参与者发生急性肾损伤这一严重AE（CKD3接受EQW治疗者，n = 1；CKD2接受吡格列酮治疗者，n = 1）。
结论
艾塞那肽每周一次在轻度和中度肾功能损害的2型糖尿病患者中耐受性良好且疗效相似。
试验注册
ClinicalTrials.gov标识符：NCT00637273、NCT00676338、NCT02229383、NCT02229396、NCT00641056、NCT01652729、NCT00935532、NCT01003184。
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