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
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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“Glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications improve health outcomes in patients with type 2 diabetes mellitus (T2DM).”
From Differences in GLP-1 RA medication adherence across place-based variables in patients with diabetes living in Wisconsin (2025) · cites this paper as [7]
In the citing paper
“The safety profile of GLP1-RAs is generally favorable with predictable gastrointestinal (GI) adverse effects that often wane over time but, in some, may lead to discontinuation of treatment.”
From The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity (2025) · cites this paper as [16]
In the citing paper
“This stepwise approach anchored in trial evidence strengthens confidence in the validity and applicability of the current results, reinforcing the role of GLP-1-based therapies beyond previously established benefits in the evolving management of cardiometabolic HFpEF.54,56-62”
From Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction (2025) · cites this paper as [57]
Citations
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Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629 · cited 5×
“We examined the association between GLP-1RA use and the positive outcome of control of weight loss, including a body mass index (BMI) decrease of 5 kg m −2 to 10 kg m −2 , and 10−30% weight loss from baseline, major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE).”
InfluentialSemaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1607141 · Cited by 6,900 · cited 1×
“…controlled trials, our results showed that GLP-1RAs reduced the risk of cardiovascular and renal outcomes, including heart failure 10 , stroke 3,7 , acute kidney injury 52 , chronic kidney disease 8,52 and the composite outcomes of MACE 2–4, 6– 8, 52 However, our results also showed a…”
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Research works printed but not linked: 1
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Cited by
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GLP-1-based therapies for diabetes, obesity and beyond
Drucker, D. J. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01183-8 · Cited by 297
Celletti, F., Farrar, J., & De Regil, L. (2026) · JAMA · doi:10.1001/jama.2025.24288 · Cited by 153
GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity
Dai, H., Li, Y., Lee, Y. A., Lu, Y., George, T. J., Donahoo, W. T., Lee, K. P., Nakshatri, H., Allen, J. M., Guo, Y. M., et al. (2025) · JAMA Oncology · doi:10.1001/jamaoncol.2025.2681 · Cited by 112
Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists
Galli, M., Benenati, S., Laudani, C., Simeone, B., Sarto, G., Ortega‐Paz, L., Rocco, E., Bernardi, M., Spadafora, L., D’Amario, D., et al. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.08.027 · Cited by 116
Rosen, C. J., & Ingelfinger, J. R. (2026) · New England Journal of Medicine · doi:10.1056/nejmra2500106 · Cited by 126
Metadata
- Authors
- Xie, Y., Choi, T., & Al-Aly, Z.
- Affiliations
- Washington University in St. Louis (US)
- VA St. Louis Health Care System (US)
- Venue
- Nature Medicine
- Published
- 2025-01-20
- Volume
- 31
- Issue
- 3
- Pages
- 951-962
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- 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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