Reasons for discontinuing tirzepatide in randomized controlled trials: A systematic review and meta-analysis.

IF 4.2 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

World Journal of Diabetes Pub Date : 2025-04-15 DOI:10.4239/wjd.v16.i4.101731

Abul Bashar Mohammad Kamrul-Hasan, Joseph M Pappachan, Deep Dutta, Lakshmi Nagendra, Mohammad Shafi Kuchay, Nitin Kapoor

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引用次数: 0

Abstract

Background: Despite therapeutic benefits, discontinuation of tirzepatide is common in randomized controlled trials (RCTs) due to adverse events (AEs) and other causes. No previous systematic reviews have explored the reasons for discontinuing tirzepatide in the RCTs.

Aim: To explore the reasons for permanent discontinuation of tirzepatide vs controls [placebo, insulin, and glucagon-like peptide-1 receptor agonists (GLP-1Ras)] in RCTs.

Methods: Relevant RCTs were systematically searched using related terms through multiple databases such as MEDLINE (via PubMed), Scopus, Cochrane Central Register, and ClinicalTrials.gov from their inception until June 20, 2024. RevMan web was used to conduct meta-analysis using random-effects models. Outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).

Results: Seventeen RCTs (n = 14645), mostly having low risks of bias, were analyzed. Compared to placebo, the risk of permanent discontinuation of the study drug was substantially lower with tirzepatide 10 mg (RR: 0.69, 95%CI: 0.51-0.93, P = 0.02) and similar with tirzepatide 5 mg (RR: 0.74, 95%CI: 0.47-1.17, P = 0.20) and 15 mg (RR: 0.94, 95%CI: 0.68-1.31, P = 0.71). Tirzepatide had identical discontinuation risks when compared to insulin at 5 mg (RR: 0.96, 95%CI: 0.75-1.24, P = 0.77) and 10 mg (RR: 1.19, 95%CI: 0.77-1.82, P = 0.44) doses, whereas such risk was higher with tirzepatide 15 mg than insulin (RR: 1.31, 95%CI: 1.03-1.67, P = 0.03). Compared to GLP-1RA, the permanent discontinuation risk was similar with tirzepatide 5 mg (RR: 0.98, 95%CI: 0.70-1.37, P = 0.90) but was higher with tirzepatide 10 mg (RR: 1.40, 95%CI: 1.03-1.90, P = 0.03) and 15 mg (RR: 1.70, 95%CI: 1.27-2.27, P = 0.0004). Tirzepatide, at all doses, had higher risks of AE-related discontinuation than insulin; such risks were only greater with higher doses of tirzepatide than with placebo or GLP-1RA. Discontinuation risk due to withdrawal by the study subjects was lower with tirzepatide than with placebo or insulin. Compared to the placebo, tirzepatide (all doses) conferred a lower risk of study drug discontinuation due to other causes not specifically mentioned.

Conclusion: The discontinuation risk is not higher in tirzepatide group than in the placebo arm. Many factors other than AEs led to drug discontinuation in the included RCTs.

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在随机对照试验中停用替西帕肽的原因：一项系统回顾和荟萃分析。

背景：尽管有治疗效果，但在随机对照试验（rct）中，由于不良事件（ae）和其他原因，停用替西帕肽是很常见的。在此之前的随机对照试验中，没有系统评价探讨替西肽停药的原因。目的：探讨随机对照试验中替西帕肽与对照组（安慰剂、胰岛素和胰高血糖素样肽-1受体激动剂（GLP-1Ras））永久停药的原因。方法：通过MEDLINE（通过PubMed）、Scopus、Cochrane Central Register和ClinicalTrials.gov等多个数据库从相关rct开始到2024年6月20日，使用相关术语对相关rct进行系统检索。采用RevMan web进行meta分析，采用随机效应模型。结果以95%置信区间（CI）的风险比（RR）表示。结果：共纳入17项rct (n = 14645)，多数偏倚风险较低。与安慰剂相比，替西帕肽10 mg组永久停药的风险显著降低（RR: 0.69, 95%CI: 0.51-0.93, P = 0.02），与替西帕肽5 mg组（RR: 0.74, 95%CI: 0.47-1.17, P = 0.20）和15 mg组（RR: 0.94, 95%CI: 0.68-1.31, P = 0.71）相似。与5 mg （RR: 0.96, 95%CI: 0.75-1.24, P = 0.77）和10 mg （RR: 1.19, 95%CI: 0.77-1.82, P = 0.44）剂量的胰岛素相比，替西帕肽的停药风险相同，而15 mg剂量的替西帕肽的停药风险高于胰岛素（RR: 1.31, 95%CI: 1.03-1.67, P = 0.03）。与GLP-1RA相比，替西帕肽5 mg组的永久停药风险相似（RR: 0.98, 95%CI: 0.70 ~ 1.37, P = 0.90），但替西帕肽10 mg组（RR: 1.40, 95%CI: 1.03 ~ 1.90, P = 0.03）和15 mg组（RR: 1.70, 95%CI: 1.27 ~ 2.27, P = 0.0004）的永久停药风险较高。在所有剂量下，替西帕肽都比胰岛素有更高的ae相关停药风险；只有高剂量的替西帕肽比安慰剂或GLP-1RA的风险更大。替西帕肽组因停药引起的停药风险低于安慰剂组或胰岛素组。与安慰剂相比，替西帕肽（所有剂量）由于其他未明确提到的原因而导致研究药物停药的风险较低。结论：替西帕肽组停药风险不高于安慰剂组。在纳入的随机对照试验中，除不良事件外，还有许多因素导致停药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

自引率

2.40%

发文量

909

期刊介绍： The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.