By Maya Menashe, Senior Science and Technology Editor
Glucagon-like peptide-1 (GLP-1) is a hormone released naturally in the gut after eating a meal whose job is to regulate blood sugar levels and metabolism. Since 2005, many pharmaceutical companies, such as Novo Nordisk (owner of the popular GLP-1 medication Wegovy) and Eli Lilly (owner of Mounjaro) have developed GLP-1 receptor agonists that mimic this hormone by binding to GLP-1 receptors throughout the body and thereby amplifying its effects. Although GLP-1 receptor agonists are a class of medications intended to lower blood sugar levels and weight in type-2 diabetic and obese patients, recent studies have shown that these medications are actually beneficial in improving the quality of life for people with serious mental illnesses (SMIs).
GLP-1 receptor agonists work through multiple coordinated mechanisms by stimulating insulin release when blood glucose rises. This suppresses glucagon, the peptide hormone that is a fast-acting regulator of blood glucose levels, to reduce excess glucose production and slowing down gastric emptying to control blood sugar spikes and increase the feeling of satiety. In the short term, this helps regulate blood sugar levels and weight gain in those with type 2 diabetes and obesity, but their long-term effects are much greater, as supported by a plethora of clinical trials. For example, one study called the LEADER trial tested the effect of liraglutide, a GLP-1 receptor agonist medication, by randomly assigning 1.8 milligrams of either the real or placebo medication to 9,340 patients with type 2 diabetes at high cardiovascular risk. After a mean follow up of 3.8 years, researchers found that there was a 13% reduction in major adverse cardiovascular events, which leads to an extended healthspan and in turn lifespan.
Several ongoing studies are now extending the benefits of GLP-1 directly to some serious mental illnesses (SMIs). Research shows that those, particularly males, with SMIs may face death 10 to even 20 years earlier than the general population. Furthermore, those who are experiencing SMIs such as schizophrenia, bipolar disorder and major depressive disorder are put onto antipsychotics to help their illnesses. However, most antipsychotics lead to rapid weight gain, which poses the original problem of cardiovascular and cerebrovascular morbidity and mortality. Therefore, researchers are now looking into whether GLP-1 drugs may have direct neuropsychiatric effects. One analysis published in February 2025 in the journal Nature Mental Health reviewed over 370 preclinical experiments on animals and clinical trials on humans that investigated the direct psychiatric effects of GLP-1 drugs. The findings suggested that GLP-1 receptors are involved in brain regions of cognition, reward and emotional regulation, thereby influencing these pathways. One factor includes oxidative stress that arises from poor lifestyle choices such as smoking and consuming alcohol. Another factor is environmental exposures such as exposure to radiation and air pollution that can cause chronic illnesses such as neurodegenerative diseases, cancer or insulin resistance that can lead to diabetes. The preclinical studies showed that activating GLP-1 receptors can reduce neuroinflammation, in turn allowing for these medications to help with learning and memory in these patients.
Further clinical studies have shown that GLP-1 receptor agonists may also possibly protect against some neurodegenerative diseases. In a study of patients with type 2 diabetes, when a select group was treated with GLP-1 medication, they had a lower incidence of dementia compared to those who took other diabetes medications. As for substance abuse patients, preclinical experiments show that GLP-1 medications may reduce their addictive behaviors by altering the brain’s dopamine system. There is not much evidence supporting the effectiveness of GLP-1 medications on individuals with mood or anxiety disorders.
Current research on GLP-1 receptor antagonists show promising effects on some SMIs. While many studies are currently underway and there are not yet strong conclusions supporting their direct psychiatric benefits, the future of psychiatry may include these medications.
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