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Mapping the effectiveness and risks of GLP-1 receptor agonists
Yan Xie1,2,3,4, Taeyoung Choi1,2, Ziyad Al-Aly5,6,7,8,9
1Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA.
Nature Medicine
|January 20, 2025
Summary
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) show benefits in reducing risks for neurological, cardiometabolic, and infectious conditions. However, GLP-1RA use is linked to increased gastrointestinal issues and other adverse events compared to usual care.
Area of Science:
- Pharmacology and Endocrinology
- Real-world evidence in chronic disease management
Background:
- Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are widely prescribed for diabetes and obesity.
- Systematic evaluation of GLP-1RA effectiveness and risks across diverse health outcomes is needed.
Purpose of the Study:
- To comprehensively assess the associations of GLP-1RA use with a wide range of health outcomes.
- To compare GLP-1RA effects against multiple antihyperglycemic agents and usual care.
Main Methods:
- Utilized US Department of Veterans Affairs databases to form large cohorts of patients with diabetes initiating GLP-1RA or comparator drugs.
- Employed a discovery approach to analyze associations with 175 health outcomes.
- Compared GLP-1RA users against sulfonylureas, DPP4 inhibitors, SGLT2 inhibitors, a combined control group, and usual care.
Main Results:
- GLP-1RA use was associated with reduced risks of substance use disorders, psychotic disorders, seizures, neurocognitive disorders, cardiometabolic disorders, and infections compared to usual care.
- Increased risks were observed for gastrointestinal disorders, hypotension, syncope, arthritic disorders, nephrolithiasis, and pancreatitis with GLP-1RA use versus usual care.
Conclusions:
- GLP-1RAs demonstrate a broad spectrum of benefits and risks in a real-world setting.
- Findings can inform clinical decision-making and future research priorities for GLP-1RA therapy.
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