In one of the most comprehensive studies of glucagon-like peptide-1 receptor agonists to date, researchers found these medications demonstrate significant protective effects across multiple body systems while identifying important risk factors requiring monitoring.
In the study, published in Nature Medicine, investigators analyzed data from over 1.9 million patients in the Department of Veterans Affairs system between October 2017 and December 2023, comparing outcomes between 215,970 glucagon-like peptide-1 receptor agonist (GLP-1 RA) users and various control groups.
Beyond their known benefits for diabetes management and weight loss, GLP-1 RAs were associated with reduced risks of:
- Substance use disorders including alcohol, cannabis, opioid, and stimulant use
- Neurocognitive disorders including Alzheimer's disease and dementia
- Seizures
- Cardiovascular events including heart failure, stroke, and cardiac arrest
- Respiratory conditions including chronic obstructive pulmonary disease and pneumonia
- Blood clotting disorders
- Liver failure
- Inflammatory bowel disease
- Sepsis.
"The data revealed broad pleiotropic effects, which may help guide clinical practice and inform future clinical and mechanistic research directions," wrote lead author Ziyad Al-Aly, MD, and colleagues.
However, the study also identified increased risks requiring clinical monitoring, including:
- Gastrointestinal disorders
- Hypotension and syncope
- Arthritic conditions
- Kidney stones
- Interstitial nephritis
- Drug-induced pancreatitis.
The investigators found GLP-1 RAs were associated with a particularly high risk of drug-induced acute pancreatitis (hazard ratio = 2.46, 95% confidence interval = 2.05–2.96).
The study's limitations included an older, predominantly white male veteran population, which may affect generalizability. The investigators also noted that their systematic analysis may have missed weaker associations that could be detected in targeted studies of specific outcomes.
The investigators suggested clinicians should consider GLP-1 RAs' broader health impacts when prescribing while implementing appropriate monitoring for identified risks. The results also highlighted multiple areas warranting further research into these medications' mechanisms of action across different organ systems.
Two authors are uncompensated consultants for Pfizer. No other potential competing interests relevant to this article were reported.
