Gao Le, Yu Shuqing, Cipriani Andrea, Wu Shanshan, Huang Yi, Zhang Zilu, Yang Jun, Sun Yixin, Yang Zhirong, Chai Sanbao, Zhang Yuan, Ji Linong, Zhan Siyan, Sun Feng
1Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
2Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK.
Aging Dis. 2019 Dec 1;10(6):1311-1319. doi: 10.14336/AD.2019.0303. eCollection 2019 Dec.
As a new class of antidiabetic drug, incretin-based therapies, which include dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have raised concerns about symptoms of withdrawal in patients with type 2 diabetes mellitus (T2DM), such as dizziness and headache. To systematically evaluate whether incretin-based therapies may lead to dizziness and headache in patients with T2DM compared to other traditional antidiabetic drugs or placebo. We searched Medline, Embase, the Cochrane library, and clinicaltrials.gov from inception through June 23, 2017, to identify randomized controlled trials of the safety of DPP-4Is or GLP-1 RAs versus placebo or other antidiabetic drugs in T2DM patients. We used the network meta-analysis under the frequentist framework to compare the association between multiple antidiabetic drugs and dizziness and headache. A total of 233 clinical trials with nine treatments and 147,710 patients were included: two incretin-based therapies, one placebo, and six traditional antidiabetic drugs (metformin, insulin, sulfonylurea, thiazolidinediones, alpha-glucosidase inhibitor, and sodium-glucose co-transporter 2). Compared to insulin, thiazolidinediones, or placebo, GLP-1 RAs statistically significantly increased the risk of dizziness (odds ratios [ORs]: 1.92, 1.57, and 1.40, respectively) and headache (ORs: 1.34, 1.41, and 1.18, respectively). DPP-4Is increased the risk of headache (OR: 1.22, 95% confidence interval [CI]: 1.02 to 1.46; moderate quality) and dizziness (OR: 1.46, 95% CI: 1.05 to 2.03; moderate quality) compared to insulin. Of the incretin-based therapies, DPP-4Is had a lower risk of dizziness than GLP-1 RAs (OR: 0.76, 95% CI: 0.67 to 0.87; high quality). Ranking probability analysis indicated that GLP-1 RAs may have the greatest risk of both dizziness and headache among the nine treatments (22.5% and 23.4%, respectively), whereas DPP-4Is were in the middle (46.2% and 45.0%, respectively). Incretin-based therapies increase the risk of dizziness and headache compared to insulin, thiazolidinediones, and placebo.
作为一类新型抗糖尿病药物，基于肠促胰素的疗法，包括二肽基肽酶-4抑制剂（DPP-4Is）和胰高血糖素样肽-1受体激动剂（GLP-1 RAs），引发了对2型糖尿病（T2DM）患者戒断症状的担忧，如头晕和头痛。为了系统评估与其他传统抗糖尿病药物或安慰剂相比，基于肠促胰素的疗法是否可能导致T2DM患者出现头晕和头痛。我们检索了从创刊至2017年6月23日的Medline、Embase、Cochrane图书馆和clinicaltrials.gov，以确定DPP-4Is或GLP-1 RAs与安慰剂或其他抗糖尿病药物在T2DM患者中安全性的随机对照试验。我们在频率学派框架下使用网络荟萃分析来比较多种抗糖尿病药物与头晕和头痛之间的关联。总共纳入了233项包含9种治疗方法和147710名患者的临床试验：两种基于肠促胰素的疗法、一种安慰剂和六种传统抗糖尿病药物（二甲双胍、胰岛素、磺脲类、噻唑烷二酮类、α-葡萄糖苷酶抑制剂和钠-葡萄糖协同转运蛋白2）。与胰岛素、噻唑烷二酮类或安慰剂相比，GLP-1 RAs在统计学上显著增加了头晕风险（优势比[ORs]：分别为1.92、1.57和1.40）和头痛风险（ORs：分别为1.34、1.41和1.18）。与胰岛素相比，DPP-4Is增加了头痛风险（OR：1.22，95%置信区间[CI]：1.02至1.46；中等质量）和头晕风险（OR：1.46，95%CI：1.05至2.03；中等质量）。在基于肠促胰素的疗法中，DPP-4Is的头晕风险低于GLP-1 RAs（OR：0.76，95%CI：0.67至0.87；高质量）。排序概率分析表明，在九种治疗方法中，GLP-1 RAs可能在头晕和头痛方面风险最大（分别为22.5%和23.4%），而DPP-4Is处于中间水平（分别为46.2%和45.0%）。与胰岛素、噻唑烷二酮类和安慰剂相比，基于肠促胰素的疗法增加了头晕和头痛的风险。
