Wake Forest School of Medicine, Winston-Salem, North Carolina.
Clin Ther. 2011 Nov;33(11):1609-29. doi: 10.1016/j.clinthera.2011.09.028. Epub 2011 Nov 8.
Oral glucose-lowering agents are used to treat patients with type 2 diabetes mellitus (T2DM). Most patients require multiple agents to maintain glycemic targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors are administered as monotherapy and in combination therapy for the treatment of T2DM.
The aim of this article was to provide a thorough review of published tolerability data on 5 DPP-4 inhibitors.
PubMed and Web of Science were searched for English-language clinical trials published from January 2000 to June 2001, using the following key words: dipeptidyl peptidase-4 inhibitor, vildagliptin, alogliptin, sitagliptin, saxagliptin, linagliptin, safety, tolerability, efficacy, effect, AE, and adverse effect. Studies were considered for inclusion if they were randomized, double-blind trials performed in patients ≥18 years of age with T2DM and with a hemoglobin A(1c) of ≥6.5%; included ≥1 arm that received monotherapy with DPP-4; and reported adverse events (AEs). Studies in patients with a history of type 1 or secondary forms of diabetes, significant diabetic complications or cardiovascular disease within the 6 months before the start of the study, hepatic disease or abnormalities, and/or renal abnormalities were excluded.
A total of 45 clinical trials, 5 pharmacokinetic studies, and 28 meta-analyses or reviews were included. The duration of studies ranged from 7 days to 104 weeks. The most commonly reported AEs were nasopharyngitis, upper respiratory infections, all-cause infections, headache, gastrointestinal symptoms, and musculoskeletal pain. Based on the findings from the studies, the DPP-4 inhibitors had minimal impact on weight and were not associated with an increased risk for hypoglycemia relative to placebo. Rates of nasopharyngitis were higher with the DDP-4 inhibitors than with placebo. Pancreatitis was reported at lower rates with the DPP-4 inhibitors compared with other oral antihyperglycemic agents. Cardiovascular events were limited, and postmarketing studies are ongoing.
The tolerability of DPP-4 inhibitors is supported by published clinical trials. The rates of weight gain, gastrointestinal AEs, and hypoglycemia were minimal with the DPP-4 inhibitors studied.
口服降糖药用于治疗 2 型糖尿病（T2DM）患者。大多数患者需要多种药物来维持血糖目标。二肽基肽酶-4（DPP-4）抑制剂可作为单一疗法和联合疗法用于治疗 T2DM。
本文旨在全面回顾已发表的 5 种 DPP-4 抑制剂的耐受性数据。
使用以下关键词在 PubMed 和 Web of Science 中搜索 2000 年 1 月至 2001 年 6 月发表的英文临床研究：二肽基肽酶-4 抑制剂、维格列汀、阿格列汀、西格列汀、沙格列汀、利格列汀、安全性、耐受性、疗效、效果、AE 和不良事件。如果研究为随机、双盲试验，纳入年龄≥18 岁的 T2DM 患者，糖化血红蛋白（HbA1c）≥6.5%；至少有 1 个接受 DPP-4 单药治疗的组；且报告了不良事件（AE），则考虑纳入研究。排除有 1 型或继发性糖尿病病史、研究开始前 6 个月内有严重糖尿病并发症或心血管疾病、肝脏疾病或异常、以及/或肾脏异常的患者。
共纳入 45 项临床研究、5 项药代动力学研究和 28 项荟萃分析或综述。研究持续时间从 7 天到 104 周不等。最常报告的 AE 是鼻咽炎、上呼吸道感染、全身感染、头痛、胃肠道症状和肌肉骨骼疼痛。根据研究结果，DPP-4 抑制剂对体重的影响较小，与安慰剂相比，低血糖风险无增加。DPP-4 抑制剂的鼻咽炎发生率高于安慰剂。与其他口服降糖药相比，DPP-4 抑制剂报告的胰腺炎发生率较低。心血管事件有限，上市后研究正在进行中。
已发表的临床试验支持 DPP-4 抑制剂的耐受性。研究中的 DPP-4 抑制剂的体重增加、胃肠道 AE 和低血糖发生率较小。
