Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients
Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients
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DOI：
10.1016/j.metabol.2009.10.007
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发表时间：
2010-06-01
影响因子：
9.8
通讯作者：
Cicero, Arrigo F. G.
中科院分区：
文献类型：
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作者：
Derosa, Giuseppe;Maffioli, Pamela;Cicero, Arrigo F. G.
该研究的目的是比较控制不良的2型糖尿病患者在吡格列酮单药治疗基础上加用西格列汀或二甲双胍对体重、血糖控制、β细胞功能、胰岛素抵抗和炎症状态参数的影响。151例未控制的2型糖尿病患者（糖化血红蛋白[HbA(1c)] >7.5%）接受吡格列酮30mg /d治疗。我们随机分配患者服用吡格列酮30毫克加西格列汀100毫克每天一次，或吡格列酮15毫克加二甲双胍850毫克每天两次。我们在基线和3、6、9和12个月后评估这些参数：体重、体重指数、HbA（1c）、空腹血糖（FPG）、餐后血糖（PPG）、空腹血浆胰岛素（FPI）、稳态模型评估胰岛素抵抗指数（HOMA-IR）、稳态模型评估β细胞功能指数、持久血浆胰岛素原（Pr）、Pr/FPI比值、脂联素、抵抗素(R)、肿瘤坏死因子- α (tnf - α)和高敏c反应蛋白。在研究结束时，二甲双胍组观察到体重和体重指数下降，而西格列汀组没有。我们观察到，与基线相比，两组患者的HbA（1c）、FPG和PPG均显著降低，体内平衡模型评估β细胞功能指数显著升高，但两组之间无显著差异。两组患者的空腹血浆胰岛素、血浆Pr、Pr/FPI比值和HOMA-IR值均降低，但二甲双胍组的数值明显低于西格列汀组。西格列汀组ADN、R和tnf - α值无显著变化，而二甲双胍组ADN显著升高，R和tnf - α值显著降低。两组患者的高敏c反应蛋白值均显著降低，两组间差异无统计学意义。吡格列酮加二甲双胍组HOMA-IR降低与ADN升高、HOMA-IR降低与R、tnf - α降低有显著相关性。在吡格列酮中加入西格列汀或二甲双胍可改善HbA（1c）、FPG和PPG；但二甲双胍也导致体重下降，促进和更好地改善胰岛素抵抗和炎症状态参数，即使西格列汀产生更好的保护β细胞功能。(C) 2010爱思唯尔公司版权所有。
The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state parameters. One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >7.5%) in therapy with pioglitazone 30 mg/d were enrolled in this study. We randomized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day, or pioglitazone 15 mg plus metformin 850 mg twice a day. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA(1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell function index, lasting plasma proinsulin (Pr), Pr/FPI ratio, adiponectin, resistin (R), tumor necrosis factor-alpha (TNF-alpha), and high-sensitivity C-reactive protein. A decrease of body weight and body mass index was observed with metformin, but not with sitagliptin, at the end of the study. We observed a comparable significant decrease of HbA(1c), FPG, and PPG and a significant increase of homeostasis model assessment beta-cell function index compared with baseline in both groups without any significant differences between the 2 groups. Fasting plasma insulin, Pasting plasma Pr, Pr/FPI ratio, and HOMA-IR values were decreased in both groups even if the values obtained with metformin were significantly lower than the values obtained with sitagliptin. There were no significant variations of ADN, R, or TNF-a with sitagliptin, whereas a significant increase of ADN and a significant decrease of R and TNF-alpha values were recorded with metformin. A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any significant differences between the 2 groups. There was a significant correlation between HOMA-IR decrease and ADN increase, and between HOMA-IR decrease and R and TNF-alpha decrease in pioglitazone plus metformin group tiller the treatment. The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA(1c) FPG, and PPG; but metformin led also to a decrease of body weight and to a foster and better improvement of insulin resistance and inflammatory state parameters, even if sitagliptin produced a better protection of beta-cell function. (C) 2010 Elsevier Inc. All rights reserved.