A recent study has illuminated the complex landscape of potential benefits and risks associated with GLP-1 receptor agonists (GLP-1RAs), medications commonly used in diabetes management. The research, which analyzed extensive records from the US Department of Veterans Affairs databases, examined the impact of GLP-1RAs on 175 health outcomes. This comprehensive study involved 215,970 individuals with diabetes who received GLP-1RAs alongside usual care, compared to 1,203,097 individuals who only received standard care. Participants were tracked over a median period of approximately 3.5 years, with an average body mass index above the obesity threshold.
The findings reveal that while GLP-1RAs are associated with a reduced risk of 42 health conditions, they also present an increased risk for 19 others. Notably, these medications, found in drugs such as Saxenda, Wegovy, and Mounjaro, showed a lower risk for conditions ranging from clotting disorders to chronic kidney disease. Researchers are also exploring the potential of GLP-1RAs in areas such as dementia and cancer.
Dr. Ziyad Al-Aly, a key researcher in the study, stated the team's intent to "map the landscape of benefits and risks."
“We wanted, literally, to map the landscape of benefits and risks,” – Dr Ziyad Al-Aly
However, the study also highlighted increased risks associated with GLP-1RAs, including abdominal pain, nausea and vomiting, low blood pressure, and kidney stones. An elevated risk of arthritis was also observed among the participants using these medications.
Dr. Al-Aly explained some of these risks as potentially stemming from rapid weight loss effects.
“This is likely related to decreased muscle mass and some deconditioning that happens in people who rapidly lose weight,” – Dr Ziyad Al-Aly
Despite these risks, the study found several significant reductions in mental health-related conditions. Individuals taking GLP-1RAs experienced reduced risks of opioid-use disorders by 13%, bulimia by 19%, schizophrenia and other psychotic disorders by 18%, suicidal ideation or self-harm by 10%, Alzheimer’s disease by 12%, and bacterial infections by 12%. These findings suggest that GLP-1RAs may offer a range of potential mental health benefits.
“This is likely related to decreased muscle mass and some deconditioning that happens in people who rapidly lose weight,” – Dr Ziyad Al-Aly
The research focused exclusively on individuals with diabetes, but Dr. Al-Aly noted that there is no biological or clinical reason to anticipate significantly different profiles for those without diabetes.
“We only studied people with diabetes but there is no biologic or clinical reason to think that the beneficial and risk profiles would be very different in people without diabetes,” – Dr Ziyad Al-Aly
Despite this, it remains unlikely that individuals without obesity would experience similar benefits. The study opens new avenues for understanding disease mechanisms and potential treatments.
“This type of analysis can teach us about mechanisms of diseases that we have not considered previously – and could open pathways to new treatments for these conditions,” – Dr Ziyad Al-Aly
Experts like Prof Naveed Sattar emphasize the importance of continued research to fully understand the safety and net benefits of GLP-1RAs.
“As more larger trials report, we will learn more about these classes of medicines, especially those that also give big weight loss, allowing us to better understand their net benefits and safety and potential widening their indications,” – Prof Naveed Sattar