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Cited by 300Diabetes Treatment and ManagementDiabetes Management and ResearchPharmacology and Obesity Treatment

The DOI matches its Crossref record; 107 of the 110 references it cites were found in a registry or an index.

Mapping the effectiveness and risks of GLP-1 receptor agonists

Xie, Yan, Choi, Taeyoung, Al-Aly, Ziyad·2025·Nature Medicine
DOI 10.1038/s41591-024-03412-w
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Abstract

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly being used to treat diabetes and obesity. However, their effectiveness and risks have not yet been systematically evaluated in a comprehensive set of possible health outcomes. Here, we used the US Department of Veterans Affairs databases to build a cohort of people with diabetes who initiated GLP-1RA (n = 215,970) and compared them to those who initiated sulfonylureas (n = 159,465), dipeptidyl peptidase 4 (DPP4) inhibitors (n = 117,989) or sodium-glucose cotransporter-2 (SGLT2) inhibitors (n = 258,614), a control group composed of an equal proportion of individuals initiating sulfonylureas, DPP4 inhibitors and SGLT2 inhibitors (n = 536,068), and a control group of 1,203,097 individuals who continued use of non-GLP-1RA antihyperglycemics (usual care). We used a discovery approach to systematically map an atlas of the associations of GLP-1RA use versus each comparator with 175 health outcomes. Compared to usual care, GLP-1RA use was associated with a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions. There was an increased risk of gastrointestinal disorders, hypotension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis and drug-induced pancreatitis associated with GLP-1RA use compared to usual care. The results provide insights into the benefits and risks of GLP-1RAs and may be useful for informing clinical care and guiding research agendas.

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Crossref · 10.1038/s41591-024-03412-w

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  1. Hernan, M. A. & Robins, J. M. Causal Inference: What If (CRC Press, 2010).

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Metadata

Authors
Xie, Y., Choi, T., & Al-Aly, Z.
Affiliations
  • Washington University in St. Louis (US)
  • VA St. Louis Health Care System (US)
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2025-01-20
Volume
31
Issue
3
Pages
951-962
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-024-03412-w
OpenAlex
W4406602151
Cited by
300
References
110
Citations by year
2026: 137 · 2025: 161
FWCI
203.24
Type
journal article
Language
en
Update notices
correction (2025-01-31)
Open access
closed
Licence
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
U.S. Department of Veterans Affairs
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
Keywords
GLP-1 receptor agonists, diabetes mellitus, obesity, drug safety, adverse drug reactions, sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, substance use, psychosis, seizures, neurocognitive disorders, Alzheimer's disease, dementia, gastrointestinal diseases, drug-induced pancreatitis, kidney stones, interstitial nephritis, veterans
MeSH terms
Glucagon-Like Peptide-1 Receptor, Sodium-Glucose Transporter 2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, Aged, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Sulfonylurea Compounds, United States, United States Department of Veterans Affairs, Treatment Outcome, Dipeptidyl-Peptidase IV Inhibitors

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