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Diabetes Care:艾塞那肽与吡格列酮联合或可替代胰岛素治疗2型糖尿病(Qatar研究)

2017-01-18 MedSci MedSci原创

对于二甲双胍和磺脲类药物控制不佳的2型糖尿病患者,吡格列酮和胰高血糖素肽1(GLP-1)受体激动剂艾塞那肽组合可能是胰岛素安全、有效的替代治疗选择。相关研究在线发表于1月17日的《糖尿病护理》杂志上。研究结果曾在去年美国新奥尔良ADA年会上公布。艾塞那肽可改善β细胞功能,而噻唑烷二酮类药物吡格列酮可改善β细胞功能和胰岛素敏感性。两药联合可以改善2型糖尿病患者的代谢缺陷。联合治疗可带来更大血糖获益尽

近日,糖尿病领域权威杂志Diabetes Care发表了一篇研究文章,这项Qatar 研究主要是为了探究艾塞那肽加上吡格列酮进行联合治疗与基础胰岛素治疗对经二甲双胍加磺脲类降糖药治疗后血糖长期控制不佳的2糖尿病患者的疗效并进行比较。

研究结果曾在去年美国新奥尔良ADA年会上公布。艾塞那肽可改善β细胞功能,而噻唑烷二酮类药物吡格列酮可改善β细胞功能和胰岛素敏感性。两药联合可以改善2型糖尿病患者的代谢缺陷。

联合治疗可带来更大血糖获益

在这项研究中,研究人员纳入了231例经二甲双胍加磺脲类降糖药治疗后血糖控制不佳(HbA1c7.5%58mmol/mol)的2糖尿病患者,并将这些研究对象进行随机化分组,分别接受吡格列酮加上每周服用艾塞那肽(联合治疗)或基础加上餐时胰岛素(胰岛素治疗)来维持糖化血红蛋白<7%53 mmol/mol)。

平均随访12个月后,联合治疗可使糖化血红蛋白显著降低从基础水平的10±0.6%86±5.2mmol/mol)降到6.1±0.1%43±0.7 mmol/mol),而接受胰岛素治疗的参与者只降到了7.1±0.1%54±0.8 mmol/mol)。联合治疗能够有效地降低HbA1c并且独立于性别、种族、体重指数或基础的糖化血红蛋白水平,相比联合治疗组患者,胰岛素治疗组的受试者有明显的增重增加,并且低血糖发生率增加了三倍。

尽管接受最大或近最大剂量的二甲双胍和磺脲类药物治疗,但基线时所有参与者HbA1c水平在7.5%以上(平均10%)。

研究人员将231例血糖控制不佳的2型糖尿病患者随机分配至每周2mg缓释艾塞那肽注射液联合每天15mg口服吡格列酮或早餐甘精胰岛素联合每餐前给予4-6单位门冬胰岛素治疗组。

6个月后,药物联合治疗组HbA1c平均水平(降至6.7%)和胰岛素治疗组(降至7.4%)HbA1c平均水平差异显著(P<0.0001)。12个月后,两组相差0.9%,18个月后相差1%(P<0.0001)。

药物联合治疗组相较于胰岛素治疗组达到ADA指南HbA1c <7.0%治疗目标的参与者比例更高(83% vs 53%,P=0.003),且药物联合治疗组达到HbA1c<6.5%的参与者比例也更高(50% vs 13%,P<0.0001)。

体重增加及低血糖事件减少但水肿增多

药物联合治疗组参与者平均体重增加量约为胰岛素治疗组平均体重增加量的一半(2.1 vs 4.2 kg,P<0.0001)。

低血糖为最常见的治疗相关不良事件。胰岛素治疗组和药物联合治疗组低血糖事件发生率分别为91%和66%。总体而言,胰岛素治疗组低血糖风险约为联合治疗组的3倍(6.6 vs.2.3例/人-年,P<0.0001)。仅有1例严重低血糖事件发生于胰岛素治疗组。

胰岛素治疗组和药物联合治疗组外周水肿发生率分别为3.4% 和9.3%。尽管症状较轻且通过远端利尿作用可以控制,但联合治疗组仍有2例参与者为此停止治疗。

共出现5例心血管事件,均发生于胰岛素治疗组。

由此可见,对于经二甲双胍加磺脲类降糖药治疗后血糖长期控制不佳的2型糖尿病患者,艾塞那肽加上吡格列酮进行联合治疗是非常安全有效的治疗选择。

原始出处

Abdul-Ghani M, Migahid O, Megahed A, Adams J, Triplitt C, DeFronzo RA, Zirie M, Jayyousi A. Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Poorly Controlled Patients With Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study. Diabetes Care. 2017 Jan 17. pii: dc161738. doi: 10.2337/dc16-1738.

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    2017-12-27 baoya
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    2017-01-20 bbjsj_1981
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