Hong Boram, Kim Haesoo, Lee Daeun, Kim Kisok
College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea.
BK21 Four Center for Forensic Pharmaceutical Sciences, Keimyung University, Daegu 42601, Republic of Korea.
Pharmaceuticals (Basel). 2025 Jul 18;18(7):1058. doi: 10.3390/ph18071058.
: Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is a well-established pharmacologic agent for inducing weight loss in individuals with obesity and is prescribed regardless of type 2 diabetes mellitus (DM) status. However, it remains unclear whether the weight-lowering efficacy of semaglutide differs significantly between individuals with and without DM. To address this question, we conducted a systematic review and meta-analysis comparing the effects of once-weekly subcutaneous semaglutide at 2.4 mg on weight loss in adults with and without DM. : A comprehensive literature search was performed using the PubMed database to identify randomized controlled trials (RCTs) involving overweight or obese adults receiving semaglutide at 2.4 mg weekly for 40 to 70 weeks. Using a random-effects model, we estimated the weighted mean differences in body weight reduction between the two groups. Nine RCTs met the inclusion criteria, among which two provided subgroup data for participants with and without DM within the same trial population. Registration number in PROSPERO: CRD420251077610. : In participants with DM (n = 4 studies), semaglutide was associated with a weighted mean body weight reduction of -6.34% (95% confidence interval: -6.98 to -5.69), with negligible heterogeneity across studies (I = 0.0%). By contrast, among participants without DM (n = 7 studies), the weighted estimate of weight loss was -11.57% (95% confidence interval: -12.94 to -10.19), with moderate heterogeneity observed (I = 63.6%). : The observed difference in weight loss efficacy between the groups was clinically meaningful. While once-weekly semaglutide at 2.4 mg elicited significant weight loss in both populations, the magnitude of effect was notably greater in those without DM. This disparity may be explained by metabolic characteristics frequently present in individuals with DM, such as insulin resistance, hyperinsulinemia, and compensatory mechanisms related to glycemic control.
司美格鲁肽是一种胰高血糖素样肽-1受体（GLP-1R）激动剂，是一种公认的用于诱导肥胖个体体重减轻的药物，无论2型糖尿病（DM）状态如何均可开具此药。然而，司美格鲁肽在有糖尿病和无糖尿病个体中的体重减轻疗效是否存在显著差异仍不清楚。为了解决这个问题，我们进行了一项系统评价和荟萃分析，比较了每周一次皮下注射2.4mg司美格鲁肽对有糖尿病和无糖尿病成年人减肥效果的影响。
使用PubMed数据库进行了全面的文献检索，以识别涉及超重或肥胖成年人的随机对照试验（RCT），这些成年人每周接受2.4mg司美格鲁肽治疗40至70周。我们使用随机效应模型估计了两组之间体重减轻的加权平均差异。9项RCT符合纳入标准，其中两项在同一试验人群中提供了有糖尿病和无糖尿病参与者的亚组数据。PROSPERO注册号：CRD420251077610。
在患有糖尿病的参与者中（n = 4项研究），司美格鲁肽与加权平均体重减轻-6.34%相关（95%置信区间：-6.98至-5.69），各研究间异质性可忽略不计（I² = 0.0%）。相比之下，在没有糖尿病的参与者中（n = 7项研究），体重减轻的加权估计值为-11.57%（95%置信区间：-12.94至-10.19），观察到中度异质性（I² = 63.6%）。
两组间观察到的减肥疗效差异具有临床意义。虽然每周一次2.4mg司美格鲁肽在两组人群中均引起显著体重减轻，但在无糖尿病者中的效果幅度明显更大。这种差异可能由糖尿病患者常见的代谢特征来解释，如胰岛素抵抗、高胰岛素血症以及与血糖控制相关的代偿机制。
