Health Outcomes and Pharmacy Practice Division, College of Pharmacy, The University of Texas, Austin, TX, USA.
Ann Pharmacother. 2012 Nov;46(11):1453-69. doi: 10.1345/aph.1R041. Epub 2012 Nov 7.
An up-to-date assessment of dipeptidyl peptidase-4 (DPP-4) inhibitors is needed to include newly available data.
To assess the efficacy and safety of DPP-4 inhibitors, including sitagliptin, saxagliptin, vildagliptin, and linagliptin, in type 2 diabetes.
We conducted a search of MEDLINE for randomized controlled trials (RCTs) of DPP-4 inhibitors in type 2 diabetes through November 2011, using the key terms sitagliptin, saxagliptin, vildagliptin, and linagliptin. We also searched for completed, but unpublished, trials at relevant web sites. RCTs were selected for meta-analysis if they (1) compared DPP-4 inhibitors with placebo or an antihyperglycemic agent; (2) had study duration of 12 or more weeks; (3) had 1 or more baseline and posttreatment efficacy and/or safety outcome; and (4) were published in English.
In 62 evaluated articles, DPP-4 inhibitors lowered hemoglobin A(1c) (A1C) significantly more than placebo (weighted mean difference [WMD] -0.76%; 95% CI -0.83 to -0.68); however, heterogeneity was substantial (I(2) = 82%). Exclusion of Japanese trials (n = 7) resulted in a reduction of heterogeneity (I(2) = 59%). In the non-Japanese RCTs (n = 55), DPP-4 inhibitors were associated with a reduction in A1C (WMD -0.65%; 95% CI -0.71 to -0.60) but higher risk of hypoglycemia (odds ratio [OR] 1.30; 95% CI 1.00 to 1.68) compared to placebo. The 7 Japanese-specific RCTs showed a greater reduction in A1C (WMD -1.67%; 95% CI -1.89 to -1.44) and a nonsignificant increase in risk of hypoglycemia (OR 1.41; 95% CI 0.51 to 3.88) with DPP-4 inhibitors versus placebo. When comparing DPP-4 inhibitors to active comparators, the I(2) was still high after deleting Japanese studies. In these 17 active comparator trials, there was no significant difference in A1C reduction (WMD 0.04%; 95% CI -0.09 to 0.16) or risk of hypoglycemia (OR 0.60; 95% CI 0.22 to 1.61) for DPP-4 inhibitors compared to other antihyperglycemics. There were similar odds of any or serious adverse events with DPP-4 inhibitors compared to placebo, but a decreased risk compared to other antihyperglycemics.
DPP-4 inhibitors were associated with a reduction in A1C with comparable safety profiles compared to placebo, but no significant difference in A1C compared to other hyperglycemics. Differences in efficacy and safety were observed between Japanese and non-Japanese patients.
需要对二肽基肽酶-4（DPP-4）抑制剂进行最新评估，以纳入新的可用数据。
评估 DPP-4 抑制剂（包括西格列汀、沙格列汀、维格列汀和利格列汀）在 2 型糖尿病中的疗效和安全性。
我们通过关键术语西格列汀、沙格列汀、维格列汀和利格列汀，在 MEDLINE 中对 2011 年 11 月前发表的 2 型糖尿病 DPP-4 抑制剂随机对照试验（RCT）进行了检索，并在相关网站上检索了已完成但未发表的试验。如果 RCT 符合以下标准，则可用于荟萃分析：（1）比较 DPP-4 抑制剂与安慰剂或抗高血糖药物；（2）研究持续时间为 12 周或更长；（3）有 1 个或更多基线和治疗后疗效和/或安全性结果；（4）用英文发表。
在 62 篇评估文章中，与安慰剂相比，DPP-4 抑制剂显著降低糖化血红蛋白（A1C）（加权均数差[WMD]-0.76%；95%置信区间[CI]-0.83 至-0.68）；但异质性很大（I2=82%）。排除日本试验（n=7）后，异质性降低（I2=59%）。在非日本 RCT 中（n=55），与安慰剂相比，DPP-4 抑制剂可降低 A1C（WMD-0.65%；95%CI-0.71 至-0.60），但低血糖风险更高（比值比[OR]1.30；95%CI 1.00 至 1.68）。7 项日本特定 RCT 显示，DPP-4 抑制剂与安慰剂相比，A1C 降低幅度更大（WMD-1.67%；95%CI-1.89 至-1.44），低血糖风险无显著增加（OR 1.41；95%CI 0.51 至 3.88）。当将 DPP-4 抑制剂与活性对照剂比较时，在删除日本研究后，I2 仍然很高。在这 17 项活性对照试验中，DPP-4 抑制剂与其他抗高血糖药物相比，A1C 降低（WMD 0.04%；95%CI-0.09 至 0.16）或低血糖风险（OR 0.60；95%CI 0.22 至 1.61）无显著差异。与安慰剂相比，DPP-4 抑制剂与安慰剂相比，任何不良反应或严重不良反应的可能性相似，但与其他抗高血糖药物相比，风险降低。
与安慰剂相比，DPP-4 抑制剂可降低 A1C，且安全性相似，但与其他抗高血糖药物相比，A1C 无显著差异。在日本和非日本患者中观察到疗效和安全性的差异。
