GLP-1 Receptor Agonists Tied to Risks and Benefits Beyond Weight Loss
TUESDAY, Jan. 21, 2025 -- For people with diabetes, the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is associated with a reduced risk for certain disorders and conditions, including neurocognitive and cardiometabolic disorders, and with an increased risk for others, including gastrointestinal and arthritic disorders, according to a study published online Jan. 20 in Nature Medicine.
Yan Xie, from the VA St. Louis Health Care System, and colleagues examined the effectiveness and risks for GLP-1 RAs. The authors used the U.S. Department of Veterans Affairs databases to build a cohort of people with diabetes who initiated a GLP-1 RA and compared them to patients initiating sulfonylureas, dipeptidyl peptidase 4 (DPP4) inhibitors, or sodium-glucose cotransporter-2 (SGLT2) inhibitors (215,970, 159,465, 117,989, and 258,614 individuals, respectively). They were also compared to a control group composed of equal proportions of individuals initiating sulfonylureas, DPP4 inhibitors, and SGLT2 inhibitors (536,068 people), as well as a control group that continued use of non-GLP-1 RA antihyperglycemics (usual care; 1,203,097 individuals). The associations of GLP-1 RA use with each comparator were examined for 175 health outcomes.
The researchers found that GLP-1 RA use compared with usual care was associated with a reduced risk for substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses, and several respiratory conditions. Conversely, GLP-1 RA use was associated with an increased risk for gastrointestinal disorders, hypertension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis, and drug-induced pancreatitis compared with usual care.
"Our discovery approach confirms previous studies and clinical trials and also uncovers previously unreported benefits and risks of GLP-1 RAs," the authors write. "The results may be useful for informing clinical care."
Two authors disclosed ties to Pfizer.
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