Silic Anja, Janez Andrej, Tomazic Janez, Karner Primoz, Vidmar Ludvik, Sharma Prem, Maticic Mojca
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Croat Med J. 2007 Dec;48(6):791-9. doi: 10.3325/cmj.2007.6.791.
To evaluate and compare effects of 48-week treatment with rosiglitazone and metformin on insulin resistance in patients infected with Human Immunodeficiency Virus (HIV) receiving highly active antiretroviral therapy (HAART), containing a protease inhibitor.
Randomized prospective controlled clinical trial enrolled 90 male patients infected with HIV and having impaired glucose tolerance and insulin resistance (fasting insulin concentration >20 mIU/L). The patients were randomly assigned into three groups; the first group receiving 4 mg rosiglitazone once a day, the second group receiving 500 mg metformin two times a day, and the third group serving as control without hypoglycemic treatment. The primary efficacy parameters were fasting plasma glucose and insulin levels compared between baseline and week. Data on insulin resistance and beta cell function were analyzed by the Homeostasis Model Assessment (HOMA).
After 48 weeks of treatment, the fasting insulin concentration (+/-standard deviation) in rosiglitazone group significantly declined from 39.0+/-3.35 to 19.7+/-3.99 mIU/L (P<0.001; 49% decrease) and in metformin group from 40.3+/-2.29 to 29.2+/-2.82 mIU/L (P<0.001; 27% decrease). HOMA indicated that rosiglitazone significantly reduced insulin resistance from 11.3+/-1.03 to 4.0+/-0.95 (P<0.001), compared with metformin which reduced it from 11.9+/-0.73 to 5.7+/-0.62 (P<0.001). Insulin resistance was significantly lower in the rosiglitazone group after 48 weeks (P<0.001). Metformin significantly improved beta cell function (from 257.3+/-21.91 to 707.4+/-207.32; P<0.001), as did rosiglitazone as well (from 261.3+/-27.98 to 403.3+/-162.50; P<0.001), but the improvement in the metformin group was significantly better (P<0.001). However, metformin was more efficient in improving beta cell function (from 257.3+/-21.91 to 707.4+/-207.32) than rosiglitazone (from 261.3+/-27.98 to 403.3+/-162.50).
Both rosiglitazone and metformin were effective and well tolerated in HIV treated with protease inhibitor-containing HAART. Rosiglitazone significantly more reduced insulin resistance, while beta cell function was significantly better in patients on metformin. Both drugs may be considered as an appropriate therapy, with rosiglitazone being a better alternative in treating insulin resistance in this patient population. ClinicalTrials.gov trial registration number: NCT00483392.
评估并比较罗格列酮和二甲双胍治疗48周对接受含蛋白酶抑制剂的高效抗逆转录病毒治疗（HAART）的人类免疫缺陷病毒（HIV）感染者胰岛素抵抗的影响。
随机前瞻性对照临床试验纳入了90例HIV感染且糖耐量受损和胰岛素抵抗（空腹胰岛素浓度>20 mIU/L）的男性患者。患者被随机分为三组；第一组每天服用4 mg罗格列酮，第二组每天服用500 mg二甲双胍两次，第三组作为对照组不进行降糖治疗。主要疗效参数为基线和第48周时的空腹血糖和胰岛素水平。通过稳态模型评估（HOMA）分析胰岛素抵抗和β细胞功能数据。
治疗48周后，罗格列酮组的空腹胰岛素浓度（±标准差）从39.0±3.35显著降至19.7±3.99 mIU/L（P<0.001；降低49%），二甲双胍组从40.3±2.29降至29.2±2.82 mIU/L（P<0.001；降低27%）。HOMA表明，罗格列酮显著降低胰岛素抵抗，从11.3±1.03降至4.0±0.95（P<0.001），而二甲双胍从11.9±0.73降至5.7±0.62（P<0.001）。48周后罗格列酮组的胰岛素抵抗显著更低（P<0.001）。二甲双胍显著改善β细胞功能（从257.3±21.91至707.4±207.32；P<0.001），罗格列酮也如此（从261.3±27.98至403.3±162.50；P<0.001），但二甲双胍组的改善更显著（P<0.001）。然而，二甲双胍在改善β细胞功能方面（从257.3±21.91至707.4±207.32）比罗格列酮（从261.3±27.98至403.3±162.50）更有效。
罗格列酮和二甲双胍对接受含蛋白酶抑制剂HAART治疗的HIV患者均有效且耐受性良好。罗格列酮显著降低胰岛素抵抗，而二甲双胍治疗的患者β细胞功能显著更好。两种药物均可被视为合适的治疗方法，罗格列酮是该患者群体治疗胰岛素抵抗的更好选择。ClinicalTrials.gov试验注册号：NCT00483392。
