Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Endocr Pract. 2024 Aug;30(8):737-745. doi: 10.1016/j.eprac.2024.05.009. Epub 2024 May 21.
Despite the growing literature, the effectiveness of liraglutide in weight management among individuals with prediabetes and in preventing the disease remains controversial. This study aims to critically evaluate the extent of liraglutide's impact on weight management in this population and assess the heterogeneity among extant studies.
A systematic literature search was conducted across MEDLINE, Embase, ClinicalTrials.gov, and the reference list of retrieved studies to identify eligible English language randomized controlled trials evaluating liraglutide's effect on weight in individuals with pre-diabetes. Non-randomized studies, studies not reporting relevant outcomes, and those conducted on patients with type 2 diabetes were excluded from this review. Outcomes included a change from baseline in absolute body weight in kg, body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), and low-density lipoprotein cholesterol levels. Additional safety outcomes were also reported. Data were analyzed using R statistical software version 4.3.1. A fixed-effect model was used when pooling crude numbers for study outcomes. Moreover, a sensitivity analysis using random-effect model was performed and heterogeneity was assessed using I statistics.
Five eligible studies were included, with a total of 1604 subjects in the liraglutide arm and 859 subjects in the control arm. Participants exposed to liraglutide showed a decrease in body weight (mean difference [MD] = -4.95 kg; 95% CI -5.16, -4.73; I = 93%), BMI (MD = -2.06 kg/m; 95%CI -2.22, -1.89; I = 97%), waist circumference (MD = -4.61 cm; 95% CI -4.79, -4.43; I = 82%), HbA1c (MD = -0.33%; 95%CI -0.34, -0.31; I = 100%), and low-density lipoprotein cholesterol levels (MD = -0.36 mmol/L; 95% CI -0.39, -0.33; I = 99%). The overall effect size remained similar when using a random-effects model for all outcomes. In addition, the rate of adverse events was higher with liraglutide when compared to the control; however, the dropout rates were relatively lower in the former arm.
While our meta-analysis suggests that liraglutide can reduce body weight, BMI, waist circumference, and HbA1c levels in individuals with pre-diabetes, the findings should be interpreted cautiously due to limitations such as the small number of trials and their short duration, and variability in dosages. Further randomized controlled trials examining long-term outcomes are essential to validate these findings and address the high heterogeneity among the studies included in this analysis.
尽管相关文献不断增加，但利拉鲁肽在糖尿病前期患者体重管理中的有效性及其预防疾病的作用仍存在争议。本研究旨在批判性地评估利拉鲁肽对该人群体重管理的影响程度，并评估现有研究之间的异质性。
通过 MEDLINE、Embase、ClinicalTrials.gov 和检索研究的参考文献列表，对评估利拉鲁肽对糖尿病前期个体体重影响的英文随机对照试验进行了系统的文献检索。本综述排除了非随机研究、未报告相关结局的研究以及针对 2 型糖尿病患者的研究。结局包括绝对体重（kg）、体重指数（BMI）、腰围、糖化血红蛋白（HbA1c）和低密度脂蛋白胆固醇水平的基线变化。还报告了其他安全性结局。使用 R 统计软件版本 4.3.1 分析数据。当对研究结局进行汇总时，使用固定效应模型。此外，还进行了随机效应模型的敏感性分析，并使用 I 统计评估异质性。
纳入了 5 项符合条件的研究，利拉鲁肽组共有 1604 名受试者，对照组有 859 名受试者。接受利拉鲁肽治疗的患者体重下降（平均差异 [MD] = -4.95 kg；95%CI -5.16，-4.73；I = 93%）、BMI（MD = -2.06 kg/m；95%CI -2.22，-1.89；I = 97%）、腰围（MD = -4.61 cm；95%CI -4.79，-4.43；I = 82%）、HbA1c（MD = -0.33%；95%CI -0.34，-0.31；I = 100%）和低密度脂蛋白胆固醇水平（MD = -0.36 mmol/L；95%CI -0.39，-0.33；I = 99%）。当对所有结局使用随机效应模型时，整体效应大小保持相似。此外，与对照组相比，利拉鲁肽组的不良反应发生率更高，但前者的脱落率相对较低。
虽然我们的荟萃分析表明利拉鲁肽可以降低糖尿病前期患者的体重、BMI、腰围和 HbA1c 水平，但由于试验数量少、持续时间短、剂量差异等限制，这些发现应谨慎解释。需要进一步的随机对照试验来检验这些发现，并解决本分析中包含的研究之间的高异质性。
