- Glucagon-like peptide-1 receptor agonists (GLP-1) drugs are a class of medications used to manage type 2 diabetes and treat obesity.
- While many drugs in this class are relatively new, researchers are rapidly learning that the drug’s benefits may extend well beyond managing average blood sugar levels and aiding in weight loss.
- Researchers recently conducted a review to examine what effects GLP-1 medications may have on cognitive functioning and mental health issues.
- The scientists found mixed results: While some studies showed the drugs offer neuroprotective benefits, other studies in the review raised the alarm that some medications in the drug class may increase depression and suicidal ideality.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs or GLP-1) medications have skyrocketed into popularity over the past few years. Pharmaceutical companies initially released the drugs Ozempic (semaglutide) and Mounjaro (tirzepatide) to help with blood sugar control in type 2 diabetes.
Since the medication also contributes to weight loss, both drugs were later released as Wegovy and Zepbound to help people with obesity. While semaglutide and tirzepatide are the most popular of the GLP-1 drugs at the moment, some other medications in this class include liraglutide and dulaglutide.
While many people who take GLP-1 medications for weight loss experience tremendous benefits from the drugs, the drugs may have other uses. For example, a recent study showed that GLP-1s may help curb binge drinking.
In a review conducted by scientists from the United Kingdom and Canada, researchers examined numerous studies to determine how these drugs affect cognitive abilities and mental health. While some studies they reviewed were positive regarding improving cognitive functioning, others had mixed results.
According to the existing research, the “function of GLP-1 agonists is to lower serum glucose levels and thereby manage metabolism in affected patients.”
GLP-1 drugs also improve blood flow to the heart and act directly on the hypothalamus to increase the sensation of being full after a meal. Besides these metabolic effects, GLP-1 drugs also appear to have an impact on brain health and mental health.
Since some studies show that GLP-1 drugs may have an impact on addictive behaviors, this makes scientists wonder what other neurological impacts the drug can have.
The researchers who conducted the new review utilized data from hundreds of clinical studies, preclinical studies, controlled trials, and meta-analyses to learn more about how GLP-1 medications impact the brain.
Some areas the scientists focused on included animal studies on Alzheimer’s and Parkinson’s diseases, dementia risk in people with a background of obesity or type 2 diabetes, and cognitive functioning tests in people with obesity or diabetes.
The researchers also looked at studies that analyzed how GLP-1 drugs affected substance abuse disorders, psychotic disorders, and mood and anxiety disorders.
GLP-1 drugs are promising in some areas and need more research in others. For instance, the review showed that GLP-1 drugs may have promising outcomes for people with dementia or other neurological disorders.
“There is also evidence for mechanisms involving a reduction of neuroinflammation, an increase in synaptic functioning, as well as the restoration of brain pathways of insulin signaling that may lead to improved memory formation and therefore a positive effect in Alzheimer’s disease and Parkinson’s disease,” note the authors.
More than 100 preclinical research studies suggests that GLP-1 drugs could protect against cognitive decline. These findings are significant to people with Alzheimer’s and Parkinson’s.
The researchers note that GLP-1 drugs offer protection by reducing harmful brain proteins, inflammation, and insulin resistance.
At the same time, the findings for clinical studies were more mixed, and long-term trials showed the possibility of a lower dementia risk with these drugs, but shorter trials did not show consistent cognitive improvements.
The review findings for how GLP-1s affect substance abuse disorders were largely promising, but the authors note that human studies are mostly in the early stages.
The studies using animal research showed that GLP-1 drugs helped reduce cravings for several substances by affecting dopamine pathways. Some of the substances tested include alcohol, nicotine, cocaine, and opioids.
The researchers were also interested in how GLP-1 drugs can protect mental health. The number of studies available in humans was limited, and the results were mixed.
The researchers noted that the use of GLP-1 drugs in people with schizophrenia spectrum conditions helped with comorbid diabetes and obesity. The researchers found this promising in terms of mitigating some of the cardiometabolic issues that antipsychotic drugs may create.
The research showed that GLP-1s can offer neuroprotective benefits in people taking mood stabilizers. However, something concerning the researchers came across in their review was people with anxiety and depression sometimes experience worsened symptoms.
Some case reports noted concerns over exenatide and semaglutide worsening depressive symptoms, and a larger study suggested a slightly increased risk of suicidal behavior with liraglutide.
“Overall, as GLP-1RAs become increasingly prescribed, further pharmacovigilance studies are warranted,” noted the authors.
Mir Ali, MD, a board-certified general surgeon, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, spoke with Medical News Today about the review.
“GLP-1 agonists appear to have applications beyond diabetes and weight loss; however, it is not easy to separate these benefits from improvement in diabetes or weight loss,” Ali comented. “In other words, it is difficult to prove that these medications provide a direct benefit, rather than a secondary benefit from either weight loss or control of diabetes.”
He said more research is needed to determine if and how GLP-1 drugs can cause mood disturbances.
“Changes in mood can occur from many sources, including weight loss, so further research is necessary to delineate the actual mechanism,” pointed out Ali. “Overall, serious side effects, such as suicidal ideations are very rare.”
“I find the reduction in inflammation most compelling. Chronic inflammation can lead to a host of medical problems, so any reduction in inflammation can be beneficial.”
– Mir Ali, MD
David Merrill, MD, a board-certified geriatric psychiatrist at Providence Saint John’s Health Center in Santa Monica, CA, and Singleton Endowed Chair in Integrative Brain Health, also spoke with MNT.
“This study adds to a growing body of evidence suggesting that GLP-1 receptor agonists—medications originally designed for diabetes and obesity—may have broader neuroprotective effects,” said Merrill.
“The findings are intriguing because they align with what we’ve seen in preclinical models and some human studies: GLP-1RAs appear to reduce neuroinflammation, improve insulin signaling in the brain, and potentially slow processes associated with cognitive decline,” he noted.
While Merrill sees potential for the future of GLP-1 drugs to be helpful outside treating type 2 diabetes and obesity, he also understands the need for more studies.
“While the data is promising, it’s still early. We need well-designed, long-term clinical trials to determine whether these drugs can be effectively used to preserve cognitive function or even treat neurodegenerative conditions like Alzheimer’s disease,” Merrill emphasized.