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ST. LOUIS — A new study reveals that popular diabetes and weight loss medications like Ozempic and Wegovy may offer unexpected health benefits, from reducing addiction risk to protecting against Alzheimer’s disease. However, these medications also come with important risks that patients and healthcare providers should carefully consider.
In one of the most comprehensive analyses to date, researchers examined health records of nearly 216,000 veterans to map out the full range of effects associated with GLP-1 receptor agonists (GLP-1RAs). This class of drugs that includes semaglutide (Ozempic, Wegovy) and liraglutide (Victoza, Saxenda).
The findings, published in Nature Medicine, reveal these medications affect far more bodily systems than previously recognized. Beyond their known benefits for blood sugar control and weight loss, GLP-1RAs appear to reduce the risk of various substance use disorders, including alcohol, cannabis, opioid, and stimulant addiction. The drugs were also linked to lower rates of psychotic disorders, seizures, and cognitive decline including Alzheimer’s disease and dementia.
Additionally, patients taking GLP-1RAs showed reduced risks of blood clotting problems, heart attacks, strokes, kidney disease, liver failure, inflammatory bowel disease, and several respiratory conditions including pneumonia and COPD (chronic obstructive pulmonary disease). The medications even appeared to decrease the likelihood of developing certain infections.
BENEFITS (with risk reductions)
Substance Use & Mental Health
- Alcohol use disorders: 11% lower
- Cannabis use disorders: 12% lower
- Stimulant use disorders: 16% lower
- Opioid use disorders: 13% lower
- Suicidal ideation/self-harm: 10% lower
- Bulimia: 19% lower
- Schizophrenia/psychotic disorders: 18% lower
Neurological
- Seizures: 10% lower
- Neurocognitive disorders: 5% lower
- Dementia: 8% lower
- Alzheimer’s disease: 12% lower
Cardiovascular & Blood
- Myocardial infarction: 9% lower
- Cardiac arrest: 22% lower
- Heart failure: 11% lower
- Ischemic stroke: 7% lower
- Hemorrhagic stroke: 14% lower
- Blood clotting disorders: 8% lower
- Deep vein thrombosis: 8% lower
- Pulmonary embolism: 12% lower
Other Systems
- Acute kidney injury: 12% lower
- Chronic kidney disease: 3% lower
- Bacterial infections: 12% lower
- Pneumonia: 16% lower
- COPD: 10% lower
- Respiratory failure: 23% lower
- Hepatic failure: 24% lower
- Inflammatory bowel disease: 12% lower
- Liver cancer: 18% lower
However, it wasn’t all good news. The study also identified several consistent side effects and risks. As many patients already know, GLP-1RAs frequently cause gastrointestinal issues like nausea, vomiting, and acid reflux. But researchers also found increased risks of low blood pressure, fainting episodes, joint pain, kidney stones, and inflammation of the kidneys. Perhaps most concerning was an elevated risk of drug-induced pancreatitis – inflammation of the pancreas that can be serious.
The research team, led by Dr. Ziyad Al-Aly at the VA St. Louis Health Care System, analyzed data from 215,970 veterans who started taking GLP-1RAs between late 2017 and 2023. They compared their health outcomes to multiple control groups: patients taking other diabetes medications and those continuing their usual care without GLP-1RAs.
GLP-1 RISKS (with risk increases)
Gastrointestinal
- Nausea and vomiting: 30% higher
- GERD (acid reflux): 14% higher
- Gastritis: 10% higher
- Noninfectious gastroenteritis: 12% higher
- Gastroparesis: 7% higher
- Diverticulosis/diverticulitis: 8% higher
- Drug-induced pancreatitis: 146% higher
Other Systems
- Hypotension (low blood pressure): 6% higher
- Syncope (fainting): 6% higher
- Sleep disturbances: 12% higher
- Headaches: 10% higher
- Arthritis: 11% higher
- Joint pain: 11% higher
- Tendinitis/synovitis: 10% higher
- Kidney stones: 15% higher
- Interstitial nephritis: 6% higher
This approach allowed researchers to evaluate the medications’ effects across 175 different health outcomes — everything from heart attacks to headaches. The median follow-up period was 3.68 years, providing insight into both short and medium-term impacts of these increasingly popular drugs.
“Given the drugs’ newness and skyrocketing popularity, it is important to systematically examine their effects on all body systems — leaving no stone unturned — to understand what they do and what they don’t do,” said Dr. Al-Aly, a clinical epidemiologist and nephrologist who treats patients at the WashU Medicine-affiliated John J. Cochran Veterans Hospital in St. Louis.
The findings could help explain mounting anecdotal reports of unexpected benefits from GLP-1RA users — like reduced alcohol cravings or improved mood — that seemed unrelated to the drugs’ effects on weight and blood sugar. The study suggests these weren’t just coincidences but rather reflect the medications’ broad influences throughout the body.
The results also raise intriguing possibilities for new therapeutic applications. Could these drugs eventually be prescribed to prevent cognitive decline or treat addiction? While more research is needed, this study provides compelling evidence for exploring these potential uses.
“Our approach has allowed us to build a comprehensive atlas mapping the associations of GLP-1RA spanning all organ systems,” he said. “The study’s results provide insights into some known and previously unrecognized benefits and risks of GLP-1RA that may be useful to inform clinical care and guide research agendas.”
For now, the findings can help doctors and patients make more informed decisions about using GLP-1RAs. The study also highlights the importance of careful monitoring for side effects, particularly those affecting blood pressure, kidney function, and the pancreas.
As these medications continue their meteoric rise in popularity, both for diabetes and weight loss, understanding their full range of effects becomes increasingly crucial. This research suggests we’ve only scratched the surface of their potential impacts on human health, for better and worse.
Paper Summary
Methodology Explained
The researchers used VA healthcare databases to identify patients who started taking GLP-1RAs and compare them to similar patients who didn’t. They carefully matched the groups based on numerous factors like age, other health conditions, and medications to ensure fair comparisons. They then tracked 175 different health outcomes over time, using statistical methods to determine which outcomes were significantly different between the groups.
Key Results
Compared to usual care, GLP-1RA users showed reduced risks of: substance use disorders (11-16% lower), Alzheimer’s disease (12% lower), heart attacks (9% lower), respiratory failure (23% lower), and liver cancer (18% lower). However, they had increased risks of: nausea/vomiting (30% higher), acid reflux (14% higher), kidney stones (15% higher), and drug-induced pancreatitis (146% higher).
Study Limitations
The study population was predominantly older white males (94.7% male, 71.2% white), potentially limiting generalizability to other groups. As an observational study, it couldn’t definitively prove cause-and-effect relationships. The research also couldn’t examine differences between specific GLP-1RA medications.
Discussion and Takeaways
The findings suggest GLP-1RAs have much broader effects than previously recognized, likely due to their influence on multiple biological pathways. This could open new therapeutic possibilities but also emphasizes the need for careful patient monitoring. The strong associations with reduced substance use disorders and cognitive decline warrant further investigation through clinical trials.
Funding and Disclosures
The study was funded by the U.S. Department of Veterans Affairs. Two authors reported being uncompensated consultants for Pfizer, with no other competing interests declared.
Publication Information
Published in Nature Medicine (January 20, 2025), DOI: https://doi.org/10.1038/s41591-024-03412-w. Authors: Yan Xie, Taeyoung Choi, and Ziyad Al-Aly from the VA St. Louis Health Care System and Washington University School of Medicine.
