二肽基肽酶-4抑制剂致关节痛风险Meta分析

Risk of arthralgia due to dipeptidyl peptidase-4 inhibitors： a Meta.analysis

目的评价二肽基肽酶-4（DPP-4）抑制剂致关节痛的风险。方法检索国内外相关数据库和网上图书馆截至2016年2月收录的DPP-4抑制剂致关节痛的RCT文献，试验组应用DPP-4 抑制剂，对照组均以安慰剂替代DPP-4 抑制剂。提取纳入文献的有关数据并进行质量评价，采用RevMan 5.3软件进行Meta分析，结果用RR及其95%CI表示。结果共22项 RCT纳入Meta分析，患者共9 927例，试验组（T）6 760例，对照组（C）3 167例，疗程为 12～206 周。西格列汀研究纳入患者954例（T 545例，C 409例），沙格列汀研究4 246例（T 2 923例，C1 323例），维格列汀研究899例（T 528例，C 371例），利格列汀研究2 624例（T 1 893例，C 731例），阿格列汀研究 1 204例（T871例，C 333例）。文献质量评价结果为A 级13篇、B级8篇。Meta分析结果显示，沙格列汀与维格列汀致关节痛的风险均高于安慰剂，差异均有统计学意义（沙格列汀：RR=1.35, 95%CI： 1.01～1.81, P=0.04；维格列汀：RR=2.80, 95%CI： 1.29～6.08, P＜0.01）。亚组分析结果显示，沙格列汀 2.5 mg/d 与二甲双胍或噻唑烷二酮类降糖药两药联用、沙格列汀10 mg/d单药治疗或联用二甲双胍、维格列汀50 mg/d致关节痛的风险均高于安慰剂，差异均有统计学意义（沙格列汀 2.5 mg/d两药联用：RR=1.74, 95%CI： 1.06～2.88, P=0.030; 沙格列汀10 mg/d：RR=1.97, 95%CI： 1.01～3.82, P=0.05；沙格列汀10 mg/d 联用二甲双胍：RR=1.86, 95%CI： 1.06～3.28, P=0.03; 维格列汀50 mg/d： RR=2.55，95%CI： 1.15～5.64, P=0.02）。西格列汀、利格列汀、阿格列汀致关节痛风险均与安慰剂相似（均P＞0.05）。结论沙格列汀和维格列汀可能增加发生关节痛的风险。合并关节疾病的2型糖尿病患者使用 DPP-4 抑制剂时可选择西格列汀、利格列汀或阿格列汀。

Objective To evaluate the risk of arthralgia due to dipeptidyl peptidase-4 （DPP-4） inhibitors.MethodsThe documents involving arthralgia due to DPP-4 inhibitors ending in February 2016 were searched from correlative data base and online library. DPP-4 inhibitors was used in the test group while placebo was used in the control group. The relevant data were collected from enrolled documents and the quality of RCTs was assessed. The software Review Manager 5.3 was used for Meta-analysis and the results were expressed in RR and 95%CI.ResultsA total of 22 RCTs were enrolled into the Meta-analysis and 9 927 patients [6 760 cases in the test group （T） and 3 167 cases in the control group（T）] were treated 12 to 206 weeks. The number of patients who were enrolled into the study on sitagliptin, saxagliptin, vildagliptin, linagliptin, and alogliptin were 954 （T： 545, C： 409）, 4 246 （T： 2 923, C：1 323） , 899 （T： 528, C： 371）, 2 624 （T： 1 893, C： 731）, and 1 204 （T： 871, C： 333）, respectively. The results of quality evaluation to all literatures showed 13 for Grade A and 8 for Grade B. The results of Meta analysis showed that the risk of arthralgia induced by saxagliptin and vildagliptin was higher than that by placebo （RR=1.35, 95%CI： 1.01-1.81, P=0.04 and RR=2.80, 95%CI： 1.29-6.08, P〈0.01）.The results of subgroup analysis showed that the risk of arthralgia induced by saxagliptin 2.5 mg/d added to metformin or TZDs, saxagliptin 10 mg/d monotherapy or added to metformin, and vildagliptin 50 mg/d was higher than that by placebo （RR=1.74, 95%CI： 1.06-2.88, P=0.03; RR=1.97, 95%CI： 1.01-3.82, P=0.05; RR=1.86, 95%CI： 1.06-3.28, P=0.03; RR=2.55, 95%CI： 1.15-5.64, P=0.02）. The risk of arthralgiadue induced by itagliptin, linagliptin, and alogliptin were similar with that by placebo（all P〉0.05）. ConclusionsSaxagliptin and vildagliptin may increase the risk of arthralgia. The patients with type 2 diabetes and joint disease should choose sitagliptin, linagliptin or alogliptin when they were using DPP-4 inhibitors.