A new study published in Nature Medicine has provided the most extensive evaluation of the health effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs). Widely prescribed for diabetes and obesity, these medications have now been linked to a reduced risk of neurocognitive disorders, cardiovascular disease, and psychiatric conditions. However, researchers also identified potential gastrointestinal, pancreatic, and kidney complications associated with their use.

A large-scale U.S. Department of Veterans Affairs data analysis assessed more than 2 million patients with type 2 diabetes. The study compared 215,970 GLP-1RA users with individuals taking sulfonylureas, dipeptidyl peptidase 4 (DPP4) inhibitors, and sodium−glucose cotransporter-2 (SGLT2) inhibitors, along with two control groups totalling over 1.7 million patients on non-GLP-1 diabetes treatments. Researchers employed a discovery approach, which systematically identifies potential health associations without prior assumptions, analysing 175 different health outcomes over a median follow-up period of about 3.7 years.

Results showed that patients using GLP-1RAs had significantly lower risks of Alzheimer’s disease and dementia, substance use disorders, and major cardiovascular events, including myocardial infarction and stroke. Additionally, reduced incidences of deep vein thrombosis, pulmonary embolism, pneumonia, and chronic obstructive pulmonary disease exacerbations were noted among GLP-1RA users. These effects suggest that the medications have broad systemic benefits, likely due to their influence on weight loss, inflammation, and direct activation of GLP-1 receptors across multiple organ systems.

However, the study also highlighted increased risks associated with GLP-1RAs, particularly gastrointestinal side effects such as gastroparesis, nausea, diarrhoea, and reflux. The study reported higher rates of nephrolithiasis, interstitial nephritis, acute pancreatitis, and syncope. 

Clinicians are encouraged to assess individual patient risks and benefits, particularly those with high cardiovascular or neurocognitive risk factors. Overall, this study affirms the importance of GLP-1RA as a key therapeutic tool in metabolic and systemic disease management. However, concerns remain about drug accessibility, cost, and the importance of lifestyle interventions alongside pharmacotherapy. Further randomized trials are recommended to confirm the effects.

References:

Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med. 2025 Jan 20. doi: 10.1038/s41591-024-03412-w. Epub ahead of print. Erratum in: Nat Med. 2025 Jan 31. DOI: 10.1038/s41591-025-03542-9. PMID: 39833406.