Map of 175 Health Outcomes for GLP-1 Drugs: Lower Dementia and Addiction Risk, Higher Pancreatitis

A large observational study published in Nature Medicine looked at 175 health outcomes at once to see which disease risks are associated with GLP-1 receptor agonists (GLP-1RAs), which are widely used to treat diabetes and obesity. It was carried out by researchers at the VA St. Louis Health Care System in the United States.

More than 210,000 users vs several comparison groups

Using the U.S. Department of Veterans Affairs database, the researchers compared 215,970 people with diabetes who newly started a GLP-1RA with people who started a sulfonylurea, a DPP-4 inhibitor or an SGLT2 inhibitor, and also with about 1.2 million people who continued existing glucose-lowering drugs (the usual-care group). They took a discovery approach that scans outcomes broadly without setting a specific hypothesis.

Compared with usual care, GLP-1RA use was associated with lower risk of substance use disorders, psychotic disorders, seizures, neurocognitive disorders including Alzheimer's disease and dementia, coagulation disorders, cardiovascular and metabolic diseases, infections and some respiratory diseases. Conversely, it was also associated with higher risk of gastrointestinal disorders, low blood pressure, fainting, joint disorders, kidney stones, interstitial nephritis and drug-induced pancreatitis.

A map of associations, not proof of causation

Its significance is that it works as a 'map' that picks out topics needing follow-up clinical trials in many areas beyond blood glucose and weight, such as the brain, addiction and the kidneys. However, because this is an observational study, it does not prove causation, and unmeasured factors may have influenced the results. Given the nature of the veterans' population, the share of men is high and the participants were limited to people with diabetes, so it is hard to apply the results directly to women or to people with obesity who do not have diabetes.