A comprehensive systematic review provides evidence that glucagon-like peptide-1 receptor agonists offer dual benefits in patients with mental illness, effectively addressing metabolic disorders while potentially improving mental health outcomes.
Breit and Hubl, from the University of Bern's Translational Research Center, examined 36 studies published between 2010 and 2024 and analyzed the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with mental illness, obesity, or type 2 diabetes (T2D).
"GLP-1 RAs are safe and effective weight loss treatments for individuals with obesity and mental illness, exerting a positive effect on mental state and quality of life," the researchers wrote.
According to the authors, mental illness and psychotropic medication use are increasingly recognized as risk factors for metabolic disorders, "such as obesity, T2D, dyslipidemia, and other cardiometabolic disorders." Indeed, they noted, a recent meta-analysis cited in the review revealed that people with severe mental disorders were 3.04 times more likely to be obese than the general population.
Among the 36 included studies, 18 specifically examined the weight-reducing effect of GLP-1 RAs in patients with mental disorders. The researchers found that GLP-1 RAs not only led to significant weight loss and improved glycemic control in patients with mental illness who were on psychotropic medications but also demonstrated a beneficial effect on mental health in patients both with and without mental disorders.
Importantly, the researchers noted that "GLP-1 RAs were not associated with a worsening of mental state, suicidality, new-onset mental illness, or increased psychiatric admissions" across the studies reviewed.
The researchers proposed several possible mechanisms for these benefits. They explained that "GLP-1 RAs might enhance neurogenesis and synaptic plasticity by preventing apoptosis and oxidation and improving mood and cognitive functions." Furthermore, they suggested that "GLP-1 might exert a modulatory effect on the release of neurotransmitters such as serotonin and dopamine that are important for the pathogenesis of MDD [major depressive disorder]."
They highlighted several promising outcomes for specific mental health conditions. In schizophrenia spectrum disorders, multiple randomized controlled trials demonstrated that GLP-1 RAs significantly improved antipsychotic-induced weight gain and glucose tolerance without worsening mental illness. For depression and bipolar disorder, studies reported reductions in depression rating scales and improvements in quality of life measures.
Two of the included studies assessed the efficacy of GLP-1 RAs in treating alcohol use disorder (AUD), and one retrospective case series revealed "a significant amelioration of AUD symptoms based on AUDIT score improvement (P < .001) following semaglutide treatment for weight reduction."
Despite these promising findings, the authors cautioned that longer-term studies with larger sample sizes are needed. "There is a need for [randomized controlled trials] with larger sample sizes, a longer treatment duration and longer follow-up periods to evaluate the long-term effect of GLP-1 RAs," they noted.
The researchers also emphasized the importance of future research to investigate GLP-1 RAs as a treatment for mental illness specifically: "It would be of great interest to conduct studies investigating the use of GLP-1 RAs with the purpose to treat mental illness in order to directly assess their use in improving mental health," they wrote.
As the use of GLP-1 RAs continues to expand beyond their original diabetes indications, this systematic review provides insights for clinicians managing patients with comorbid mental illness and metabolic disorders and suggests these medications may offer benefits that address both physical and mental health challenges.
The authors declared no competing interests.
Source: Psychoneuroendocrinology