Several years ago, a little-known drug named Ozempic - previously used only to treat diabetes - emerged as a promising new drug for weight management.
Author
- Ziyad Al-Aly
Clinical Epidemiologist, Washington University in St. Louis
The Food and Drug Administration's approval of Ozempic in 2021 for weight loss treatment ushered in a new era for the class of drugs called glucagon-like peptide-1 agonists , or GLP-1.
Today, GLP-1 drugs, including Wegovy, Mounjaro and Zepbound, have become household names and key tools in the fight against obesity: 1 in 8 American adults say they have used a GLP-1 drug, and forecasts show that by 2030, 1 in 10 Americans will likely be using these medications .
Now, research from my lab and others suggests that GLP-1 drugs could help treat dozens of other ailments as well, including cognitive issues and addiction problems. However, my colleagues and I also found previously unidentified risks.
I am a physician-scientist and I direct a clinical epidemiology center focused on addressing public health's most urgent questions. My team works to address critical knowledge gaps about COVID-19, long COVID, influenza, vaccines, effectiveness and risks of commonly used drugs, and more.
On Jan. 20, 2025, my team published a study of more than 2.4 million people that evaluated the risks and benefits of GLP-1 drugs across 175 possible health outcomes. We found that these drugs lowered risks of 42 health outcomes, nearly a quarter of the total that we analyzed. These include neurocognitive disorders such as Alzheimer's disease and dementia, substance use and addiction disorders, clotting disorders and several other conditions.
Unfortunately, we also found that GLP-1 drugs come with significant side effects and increase the risk of 19 health conditions we studied, such as gastrointestinal issues, kidney stones and acute pancreatitis , in which the pancreas becomes inflamed and dysfunctional.
Cognitive benefits
One of the most important health benefits we found was that the GLP-1 drugs lowered the risk of neurodegenerative disorders, including Alzheimer's disease and dementia. These findings align with other research, including evidence from preclinical studies showing that these drugs may reduce inflammation in the brain and enhance the brain's ability to form and strengthen connections between its cells, improving how they communicate with one another. These effects contribute to mitigating cognitive decline.
Two other key studies have shown that patients treated with a GLP-1 drug for diabetes had a lower risk of dementia .
All of these studies strongly point to a potential therapeutic use of GLP-1 drugs in treatment of the cognitive decline. Ongoing randomized trials - the gold standard for evaluating new uses of drugs - are looking at the effects of GLP-1 drugs in early Alzheimer's disease, with results expected later in 2025.
Curbing addiction and suicidal ideation
GLP-1 drugs have also demonstrated potential in reducing risks of several substance use disorders such as those involving alcohol , tobacco , cannabis, opioids and stimulants. This may be due to the ability of these drugs to modulate reward pathways, impulse control and inflammatory processes in the brain.
The effectiveness of GLP-1 drugs in curbing addictive behavior may explain their spectacular success in treating obesity, a chronic disease state that many have suggested is indeed a food addiction disorder .
Our study demonstrated a reduced risk of suicidal thoughts and self-harm among people using GLP-1 drugs. This finding is particularly significant given earlier reports of suicidal thoughts and self-injury in people using GLP-1 drugs. In response to those reports, the European Medicines Agency conducted a review of all available data and concluded that there was no evidence of increased risk of suicidality in people using GLP-1 drugs.
Now at least two studies, including our own, show that GLP-1 drugs actually reduce the risk of suicidality .
Other benefits
In addition to the well-documented effects of GLP-1 drugs in reducing risks of adverse cardiovascular and kidney outcomes , our study shows a significant effect in reducing risk of blood clotting as well as deep vein thrombosis and pulmonary embolism.
One puzzling finding in our study is the reduced risk of infectious diseases such as pneumonia and sepsis. Our data complements another recent study that came to a similar conclusion showing that GLP-1 drugs reduced risk of cardiovascular death and death due to infectious causes , primarily COVID-19.
This is especially important since COVID-19 is regarded as a significant cardiovascular risk factor . Whether GLP-1 drugs completely offset the increased risk of cardiovascular disease associated with COVID-19 needs to be thoroughly evaluated.
GLP-1 drugs may also be useful in treating fatty liver disease and conditions ranging from asthma to chronic obstructive pulmonary disease , sleep apnea, osteoarthritis , depression and eye disorders.
Risks and challenges
Despite their broad therapeutic potential, GLP-1 drugs are not without risks.
Gastrointestinal issues, such as nausea, vomiting, constipation and gastroesophageal reflux disease are among the most common adverse effects associated with GLP-1 drugs.
Our study also identified other risks, including low blood pressure, sleep problems, headaches, formation of kidney stones, and gall bladder disease and diseases associated with the bile ducts . We also saw increased risks of drug-induced inflammation of the kidneys and pancreas - both serious conditions that can result in long-term health problems. These findings underscore the importance of careful monitoring in people who are taking GLP-1 medications.
A significant challenge with using GLP-1 drugs is the high rates at which patients stop using them , often driven by their exorbitant cost or the emergence of adverse effects. Discontinuation can lead to rapid weight gain.
That's a problem, because obesity is a chronic disease. GLP-1 drugs provide effective treatment but do not address the underlying causes of obesity and metabolic dysfunction. As a result, GLP-1 drugs need to be taken long term to sustain their effectiveness and prevent rebound weight gain.
In addition, many questions remain about the long-term effectiveness and risks of these drugs as well as whether there are differences between GLP-1 formulations. Addressing these questions is critical to guide clinical practice.
Ziyad Al-Aly receives funding from U.S. Department of Veterans Affairs.
