ArticleNature metabolism2026
Association of GLP-1RA discontinuation and risk of depressive and anxiety disorders in people with type 2 diabetes: a cohort study.
Tingyu Zhang, Ping He, Yunxi Ji, Juan Shi, Zizheng Zhang, Kan Wang, Haolei Pan, Huayan Yao, Yanbin Xue, Ruizhi Zheng and 5 more
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In one paragraphArticle in Nature metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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15 authors.
Tingyu Zhang *Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0009-0004-4678-5197 Ping He *Link Healthcare Engineering and Information Department, Shanghai Hospital Development Center, Shanghai, China.
Yunxi Ji *Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Juan Shi *Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0003-2652-8084 Zizheng ZhangDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kan WangDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Haolei PanDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Huayan YaoComputer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yanbin XueComputer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ruizhi ZhengDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-2068-7597 Qingxia WuWonders Information Co., Ltd., Shanghai, China.
Bin CuiDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. cb11302@rjh.com.cn.ORCID http://orcid.org/0000-0002-7293-5740 Yifei ZhangDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. feifei-a@163.com.ORCID http://orcid.org/0000-0003-0272-0602 Weiqing WangDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wqingw61@163.com.ORCID http://orcid.org/0000-0003-0197-3106 Guang NingDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. gning@sibs.ac.cn.ORCID http://orcid.org/0000-0002-5754-7635 Funding
No grant is acknowledged in the PubMed record.
6 · The paper itselfAbstract
The psychiatric safety profile of glucagon-like peptide-1 receptor agonists (GLP-1RAs) is characterized by inconsistent findings during active treatment and remains largely unexplored after cessation. Here we show that GLP-1RA discontinuation is associated with an increased risk of psychiatric events. Using large-scale electronic health records from the Shanghai Hospital Link Database, we investigate incident depressive and anxiety disorders during GLP-1RA treatment and after its discontinuation in people with type 2 diabetes, compared with dipeptidyl peptidase-4 inhibitors (DPP4is) or sodium-glucose cotransporter-2 inhibitors (SGLT2is). During treatment, GLP-1RAs show a neutral risk compared with DPP4is and a lower risk compared with SGLT2is. In contrast, after cessation, prior use of GLP-1RAs is associated with a higher risk than prior use of DPP4is or SGLT2is. This increase is modestly mediated by elevated triglyceride levels. These findings highlight the need for clinical vigilance regarding anxiety following GLP-1RA discontinuation.
Indexed as
Anxiety DisordersDepressive DisorderDiabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsCohort StudiesDipeptidyl-Peptidase IV InhibitorsFemaleHumansMaleSodium-Glucose Transporter 2 InhibitorsDipeptidyl-Peptidase IV InhibitorsGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsSodium-Glucose Transporter 2 Inhibitors
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