Evaluating the causal effect of using glucagon-like peptide-1 receptor agonists on the risk of autoimmune diseases

Yuming Sun; Qian Zhou; Lorraine Edna Onzere; Yating Dian; Yu Meng; Daishi Li; Furong Zeng; Shaorong Lei; Guangtong Deng

doi:10.1016/j.dsx.2025.103186

Evaluating the causal effect of using glucagon-like peptide-1 receptor agonists on the risk of autoimmune diseases

Diabetes Metab Syndr. 2025 Jan 7;19(1):103186. doi: 10.1016/j.dsx.2025.103186. Online ahead of print.

Authors

Yuming Sun¹, Qian Zhou², Lorraine Edna Onzere³, Yating Dian², Yu Meng², Daishi Li², Furong Zeng⁴, Shaorong Lei⁵, Guangtong Deng⁶

Affiliations

¹ Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, China; Furong Laboratory, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Oncology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: zengfurong@csu.edu.cn.
⁵ Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, Changsha, China. Electronic address: leishaorong@csu.edu.cn.
⁶ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China. Electronic address: dengguangtong@outlook.com.

PMID: 39793280
DOI: 10.1016/j.dsx.2025.103186

Abstract

Objective: To investigate the causal association of using glucagon-like peptide-1 receptor (GLP1R) agonists with autoimmune diseases.

Methods: The available cis-eQTLs for drugs target genes (GLP1R) were used as genetic variants for exposure to GLP1R agonists. Type 2 diabetes was used as positive control. Mendelian randomizations (MR) were performed to explore the association of genetically-proxied GLP1R agonists with 11 autoimmune diseases from large-scale consortia. Replicating the findings in the FinnGen study and then pooled with meta-analysis. Finally, we performed MR analysis to examine whether GLP1R agonists affect 731 immune cell phenotypes to clarify the potential mechanism.

Results: We observed supportive evidence to support the association of GLP1R agonists with reduced the risk of hypothyroidism (OR [95 %] = 0.89 [0.82-0.95], P < 0.001), but increased risk of ulcerative colitis (OR [95 %] = 1.48 [1.27-1.71], P < 0.001), type 1 diabetes (OR [95 %] = 1.34 [1.21-1.50], P < 0.001), systemic lupus erythematosus (OR [95 %] = 1.61 [1.29-2.02], P < 0.001) and sarcoidosis (OR [95 %] = 1.38 [1.08-1.75], P = 0.008). There was no supporting evidence to verify the association of GLP1R expression with asthma, Crohn's disease, multiple sclerosis and myasthenia gravis (P > 0.05). In addition, we found that GLP1R agonists was positively associated with 221 immune cell phenotypes (P < 0.05, OR > 1), and negatively associated with 317 immune cell phenotypes (P < 0.05, OR < 1).

Conclusion: GLP1R agonists are causally associated with various autoimmune diseases potentially through the modulation of 731 immune cell phenotypes.

Keywords: Autoimmune disease; GLP1R agonists; Mendelian randomization.