Drug Safety and Risk Management Department, Executive Directorate of Pharmacovigilance, Drug Sector, Saudi Food and Drug Authority, Riyadh, Saudi Arabia.
Ther Innov Regul Sci. 2024 Jul;58(4):622-633. doi: 10.1007/s43441-024-00637-2. Epub 2024 Apr 18.
Linagliptin is an oral dipeptidyl peptidase DPP-4 inhibitor, which is indicated for the treatment of Type 2 diabetes mellitus (T2DM) as monotherapy or add-on to therapy with other hypoglycemic drugs.
We aimed to summarize the evidence from randomized controlled trials (RCTs) to assess the safety of linagliptin focusing on cardiovascular risks among subjects with type 2 diabetes mellitus.
We conducted a systematic search across the following databases: Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to November 2021. Randomized controlled trials (RCTs) of linagliptin compared to placebo in patients with Type 2 diabetes were included. The primary safety points were cardiovascular (CV) adverse events including non-fatal stroke, non-fatal myocardial infarction (MI), CV death, MI, stroke, and hospitalization for unstable angina. While, secondary safety points included 17 reported adverse events such as infections, hypoglycemia and abdominal pain. Three reviewers independently screened and reviewed each study to extract relevant information. Any discrepancies were resolved by consensus. We conducted a meta-analysis using the random effects model. Pooled risk ratios (RRs) of targeted adverse events with linagliptin compared to placebo were estimated using the Mantel-Haenszel test.
A total of 24 studies with 19,981 adult patients were included. There was no difference in the incidence of all CV adverse events or individual CV adverse events between linagliptin and the placebo arms. The pooled estimate of the risk of upper respiratory tract infection was reported in twelve trials with a 38% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.62, 95% CI: 0.45-0.85, and I = 0%), while no difference was found in other infections. For gastrointestinal disorders, the risk of abdominal pain showed a 65% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.35, 95% CI: 0.16-0.77, and I = 0%).
Our study showed an overall acceptable safety profile of linagliptin in patients with T2DM. Moreover, our study showed a risk reduction of upper respiratory tract infection and abdominal pain when using linagliptin compared to placebo.
利拉利汀是一种口服二肽基肽酶 4（DPP-4）抑制剂，适用于作为单药治疗或与其他降血糖药物联合治疗 2 型糖尿病（T2DM）。
我们旨在汇总来自随机对照试验（RCT）的证据，评估利拉利汀的安全性，重点关注 T2DM 患者的心血管风险。
我们对以下数据库进行了系统检索：从建库到 2021 年 11 月的 Medline、Embase、Cochrane 对照试验中心注册库和 ClinicalTrials.gov。纳入了利拉利汀与安慰剂在 T2DM 患者中的 RCT 研究。主要安全性终点是心血管（CV）不良事件，包括非致命性中风、非致命性心肌梗死（MI）、CV 死亡、MI、中风和不稳定型心绞痛住院。次要安全性终点包括 17 种报告的不良事件，如感染、低血糖和腹痛。三名评审员独立筛选和审查了每项研究以提取相关信息。任何分歧均通过协商解决。我们使用随机效应模型进行了荟萃分析。使用 Mantel-Haenszel 检验估计利拉利汀与安慰剂相比靶向不良事件的汇总风险比（RR）。
共有 24 项研究纳入了 19981 名成年患者。利拉利汀组和安慰剂组之间所有 CV 不良事件或个别 CV 不良事件的发生率无差异。在 12 项研究中报告了上呼吸道感染的风险估计值，与安慰剂组相比，利拉利汀组患者的风险降低了 38%（RR=0.62，95%CI：0.45-0.85，I=0%），而其他感染则无差异。对于胃肠道疾病，与安慰剂组相比，利拉利汀组腹痛的风险降低了 65%（RR=0.35，95%CI：0.16-0.77，I=0%）。
我们的研究表明，利拉利汀在 T2DM 患者中的总体安全性可接受。此外，与安慰剂相比，我们的研究表明使用利拉利汀可降低上呼吸道感染和腹痛的风险。
