The effect of subcutaneous dulaglutide on weight loss in patients with Type 2 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation Pub Date : 2023-11-11 DOI:10.1111/eci.14125

Yang Li, Xingji Gong, Mihnea-Alexandru Găman, Benjamin Hernández-Wolters, Periyannan Velu, Yushan Li

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Abstract

Background

Dulaglutide, a subcutaneously administered glucagon-like peptide 1 receptor agonist, has been hypothesized to lead to weight loss in patients with Type 2 diabetes mellitus (T2DM). However, the consequences of its prescription on body weight (BW) and other anthropometric indices, for example, body mass index (BMI) or waist circumference (WC), have not been completely clarified. Therefore, we aimed to assess the effects of subcutaneous dulaglutide administration on BW, BMI and WC values in T2DM subjects by means of a systematic review and meta-analysis of RCTs.

Methods

We computed a literature search in five databases (PubMed/Medline, Web of Science, EMBASE, Scopus and Google Scholar) from their inception to February 2023 to identify RCTs that examined the influence of subcutaneous dulaglutide on obesity indices. We calculated effect sizes using the random-effects model (using DerSimonian-Laird method). Results were derived across weighted mean differences (WMD) and 95% confidence intervals (CI). Subgroup analyses were applied to explore possible sources of heterogeneity among the RCTs. The current systematic review and meta-analysis was conducted in compliance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Results

In total, 18 studies with 33 RCT arms (BW = 33 RCT arms, 14,612 participants, 7869 cases and 6743 controls; BMI = 10 RCT arms, 14,612 subjects, 7869 cases and 6743 controls; WC = 10 RCT arms, 1632 participants, 945 cases and 687 cases) were included in the meta-analysis. BW (WMD: −0.86 kg, 95% CI: −1.22, −0.49, p < 0.001), BMI (WMD: −0.68 kg/m², 95% CI: −0.88, −0.49, p < 0.001) and WC (WMD: −1.23 cm, 95% CI: −1.82, −0.63, p < 0.001) values decreased notably following subcutaneous dulaglutide administration versus placebo. BW notably decreased in RCTs lasting >18 weeks (WMD: −1.42 kg, 95% CI: −1.90, −0.94, p < 0.001), whereas notable reductions in WC were seen in RCTs lasting ≤18 weeks (WMD: −1.78 cm, 95% CI: −2.59, −0.98, p < 0.001). Dulaglutide dosages >1 mg/day significantly decreased BW (WMD: −1.94 kg, 95% CI: −2.54, −1.34, p < 0.001), BMI (WMD: −0.80 kg/m², 95% CI: −1.07, −0.54, p < 0.001) and WC (WMD: −1.47 cm, 95% CI: −1.80, −1.13, p < 0.001). BW decreased particularly following dulaglutide prescription in individuals with obesity (WMD: −1.05 kg, 95% CI: −1.28, −0.82, p < 0.001) versus overweight. The dose–response meta-analysis revealed that BW decreased significantly when dulaglutide was prescribed in doses ≤3 mg/day versus >3 mg/day.

Conclusions

Subcutaneous dulaglutide administration in T2DM reduces BW, BMI and WC. The decrease in BW and WC was influenced by the dose and the duration of dulaglutide administration. The reduction in BMI was only influenced by the dosage of dulaglutide. Moreover, T2DM patients who suffered from obesity experienced a notable decrease in BW versus T2DM subjects without obesity.

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皮下注射杜拉鲁肽对2型糖尿病患者减肥的影响：随机对照试验的系统综述和荟萃分析。

背景：杜拉鲁肽是一种皮下给药的胰高血糖素样肽1受体激动剂，据推测可导致2型糖尿病（T2DM）患者的体重减轻。然而，其处方对体重（BW）和其他人体测量指标的影响，例如体重指数（BMI）或腰围（WC），尚未完全阐明。因此，我们旨在评估杜拉鲁肽皮下给药对BW的影响，通过随机对照试验的系统回顾和荟萃分析，对T2DM受试者的BMI和WC值进行研究。方法：我们计算了从成立到2023年2月在五个数据库（PubMed/Medline、Web of Science、EMBASE、Scopus和Google Scholar）中的文献检索，以确定检查皮下杜拉鲁肽对肥胖指数影响的随机对照试验。我们使用随机效应模型（使用DerSimonian-Laird方法）计算效应大小。结果是通过加权平均差（WMD）和95%置信区间（CI）得出的。应用亚组分析来探索随机对照试验之间异质性的可能来源。目前的系统综述和荟萃分析是根据系统综述和元分析的首选报告项目（PRISMA）声明进行的。结果：总共有18项研究涉及33个随机对照试验组（BW = 33个随机对照试验组，14612名参与者，7869个病例和6743个对照组；BMI = 10个随机对照试验组，14612名受试者，7869名病例和6743名对照组；WC = 10个随机对照试验组，1632名参与者，945例和687例）纳入荟萃分析。BW（WMD:-0.86 kg，95%置信区间：-1.22，-0.49，p 2，95%可信区间：-0.88，-0.49，p 18 周（大规模杀伤性武器：-1.42 kg，95%置信区间：-1.90，-0.94，p 1. mg/天显著降低BW（WMD:-1.94 kg，95%置信区间：-2.54，-1.34，p 2，95%可信区间：-1.07，-0.54，p 3. 结论：2型糖尿病患者皮下注射杜拉鲁肽可降低体重、BMI和WC。BW和WC的降低受杜拉鲁肽给药的剂量和持续时间的影响。BMI的降低仅受杜拉鲁肽剂量的影响。此外，与未肥胖的T2DM受试者相比，患有肥胖症的T2DM患者的BW显著降低。

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来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.