Assessing the Therapeutic Potential of GLP-1 Receptor Agonists in Psoriasis and Other Skin Diseases: Insights From a Scoping Review and Mendelian Randomization Study

IF 1 4区医学 Q1 DERMATOLOGY

Dermatologic Therapy Pub Date : 2026-08-30 DOI:10.1155/dth/9612721

Xiafan Long, Yixuan Qiu, Zexu Lin, Yutong Liu, Jing Fang, Ye Wang, Yue Li, Yutong Sun, Shihan Zeng, Kai Huang

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引用次数: 0

Abstract

Background

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for diabetes and obesity, possess anti-inflammatory and tissue-reparative properties. Their dermatological relevance is increasingly recognized, but the available evidence remains heterogeneous and lacks integrated evaluation with exploratory genetic evidence.

Objective

To map the clinical evidence landscape of GLP-1RAs in skin diseases and to investigate the genetically predicted association between GLP-1 receptor (GLP-1R) signaling and dermatological outcomes.

Methods

We performed an updated scoping review of published clinical evidence integrated with a two-sample Mendelian randomization (MR) analysis. The MR analysis utilized large-scale plasma proteome genome-wide association study data (n = 35,559) and FinnGen datasets. Mediation analyses incorporating 1091 blood metabolites and 91 inflammatory proteins were conducted to explore potential underlying pathways.

Results

The updated scoping review included 113 published studies. Psoriasis/psoriatic disease, diabetic foot ulcers, and hidradenitis suppurativa represented major beneficial-effect categories, whereas cutaneous adverse events such as dermal hypersensitivity reactions and hair loss were also frequently reported. Building upon these clinical findings, our exploratory MR analysis showed that genetically predicted GLP-1R levels were nominally associated with lower psoriasis vulgaris risk (OR = 0.29; 95% CI = 0.10–0.80; p = 0.017). Mediation analysis suggested a potential overall association between GLP-1R and psoriasis risk (OR = 0.986; 95% CI = 0.976–0.997; p = 0.014), with possible mediation by metabolites including 3-hydroxydodecanedioate (mediation proportion, 6.8%) and the mannose-to-fructose ratio (5.3%), as well as the inflammatory protein interleukin-9 (−5.7%).

Conclusions

This integrative study synthesizes evidence from a scoping review and exploratory genetic analysis, suggesting a potential protective association between GLP-1R signaling and psoriasis. The findings support further investigation of incretin-based strategies in psoriatic disease and provide hypothesis-generating genetic insights into potential metabolic and inflammatory mechanisms.

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评估GLP-1受体激动剂治疗牛皮癣和其他皮肤病的潜力：来自范围回顾和孟德尔随机研究的见解

胰高血糖素样肽-1受体激动剂（GLP-1RAs）具有抗炎和组织修复特性，广泛用于糖尿病和肥胖。它们的皮肤病学相关性越来越被认识到，但现有的证据仍然是异质的，缺乏与探索性遗传证据的综合评估。目的绘制GLP-1RAs在皮肤病中的临床证据图谱，探讨GLP-1受体（GLP-1R）信号传导与皮肤病预后的遗传预测关系。方法：我们对已发表的临床证据进行了更新的范围综述，并结合了双样本孟德尔随机化（MR）分析。MR分析利用大规模血浆蛋白质组全基因组关联研究数据（n = 35,559）和FinnGen数据集。采用1091种血液代谢物和91种炎症蛋白进行中介分析，以探索潜在的潜在途径。更新的范围综述包括113项已发表的研究。牛皮癣/银屑病、糖尿病足溃疡和化脓性汗腺炎是主要的有益效果类别，而皮肤不良事件，如皮肤过敏反应和脱发也经常被报道。基于这些临床发现，我们的探索性MR分析显示，基因预测的GLP-1R水平名义上与较低的寻常型牛皮癣风险相关（OR = 0.29; 95% CI = 0.10-0.80; p = 0.017）。中介分析表明，GLP-1R与牛皮癣风险之间存在潜在的整体关联（OR = 0.986; 95% CI = 0.976-0.997; p = 0.014），可能是代谢物介导的，包括3-羟基十二烷二酸酯（中介比例6.8%）、甘露糖与果糖比（5.3%）以及炎症蛋白白介素-9（- 5.7%）。这项综合研究综合了范围综述和探索性遗传分析的证据，表明GLP-1R信号传导与牛皮癣之间存在潜在的保护性关联。这些发现支持进一步研究以肠促胰岛素为基础的银屑病治疗策略，并为潜在的代谢和炎症机制提供假设生成遗传学见解。

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

Dermatologic Therapy 医学-皮肤病学

CiteScore

7.00

自引率

8.30%

发文量

711

审稿时长

3 months

期刊介绍： Dermatologic Therapy has been created to fill an important void in the dermatologic literature: the lack of a readily available source of up-to-date information on the treatment of specific cutaneous diseases and the practical application of specific treatment modalities. Each issue of the journal consists of a series of scholarly review articles written by leaders in dermatology in which they describe, in very specific terms, how they treat particular cutaneous diseases and how they use specific therapeutic agents. The information contained in each issue is so practical and detailed that the reader should be able to directly apply various treatment approaches to daily clinical situations. Because of the specific and practical nature of this publication, Dermatologic Therapy not only serves as a readily available resource for the day-to-day treatment of patients, but also as an evolving therapeutic textbook for the treatment of dermatologic diseases.