GLP-1 Usage Does Not Increased Risk of Psychiatric Events, Study Finds
Glucagon-like peptide-1 receptor agonists have been associated with improvements in quality of life (QOL), restrained eating, and emotional eating behavior.
Glucagon-like peptide-1 (GLP-1) receptor agonists have not been associated with an increased risk of psychiatric events or worsening depression compared to the placebo. In fact, GLP-1s have been associated with improvements in quality of life (QOL), restrained eating, and emotional eating behavior, according to results of a study published in JAMA Psychiatry.1
Glucagon-like peptide-1 receptor agonists have been associated with improvements in quality of life (QOL), restrained eating, and emotional eating behavior. | Image Credit: Edugrafo - stock.adobe.com
In a study published in BMJ, GLP-1s were not associated with an increased risk of suicide compared with dipeptidyl peptidase-4 (DPP-4) or sodium-glucose cotransporter-2 inhibitors for patients with type 2 diabetes, despite concerns that GLP-1s could increase the risk of suicidal ideology. In the study, investigators found that there were only 301 suicidality events over 77,377 person-years compared with 1087 events over 599,271 person-years for those using DPP-4 inhibitors.2
However, in another study, investigators found that GLP-1 treatment was associated with a 98% increased risk of any psychiatric disorder, including 195% for major depression, 108% for anxiety, and 106% for suicidal behavior. GLP-1 medication is also being studied as a drug to reduce depression, with another study finding that the baseline depression rating scale scores decreased significantly for patients receiving GLP-1 treatment.3,4
In the current study, investigators aimed to gather evidence from randomized, double-blind, placebo-controlled trials for patients with overweight, obesity, and/or diabetes and the mental health outcomes when taking GLP-1 medications. They searched PubMed, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials databases from inception to June 24, 2024. They evaluated the risk of psychiatric adverse events, changes in validated psychiatric and mental health-related quality of life, and cognitive scales.1
There was a total of 19,909 identified, but 80 articles included a total of 107,860 patients. The mean age across studies was 60.1 years, with 40.1% of patients being female. Approximately 62% included patients with type 2 diabetes, 29% included patients with overweight/obesity, and 9% included patients with type 1 diabetes. The most studied drug was liraglutide (30%), followed by semaglutide (24.7%). For the risk of psychiatric events in general, 64 studies were used for the meta-analysis, with 30 for serious adverse events (AEs) and 37 for nonserious AEs. Serious AEs reported included major depression, suicidality, and psychosis, and nonserious events included anxiety and insomnia.1
Investigators found no significant difference in rates of serious psychiatric AEs or nonserious AEs between GLP-1s and the placebo. In the changes in psychiatric symptomology analysis, 14 studies were included, which covered depression, eating behaviors, anxiety, and suicidality. However, only depression and eating behaviors had sufficient studies for the analysis, with investigators finding no evidence for changes in depression symptoms with GLP-1s compared with the placebo. However, GLP-1 was associated with improved eating restraint and emotional eating, but not external eating/disinhibition.1
For QOL, 41 studies were included. GLP-1s were associated with improved mental health, physical health, diabetes, and weight-related QOL, as well as overall QOL, with moderate certainty for all, according to the study authors. Physical health QOL had the greatest improvements for obesity studies, but there were no differences for obesity and diabetes studies for mental health or weight QOL. Furthermore, there was not a significant association between change in mental health-related QOL with variables or magnitude of weight or hemoglobin A1c change. Physical health-related QOL was greater for female patients, those with greater weight loss, and those with lower mean age. For weight-related QOL, greater improvements were seen with a larger magnitude of weight loss, and hemoglobin A1c had greater diabetes-related QOLD improvements.1
“Our study found an association between GLP1-RA treatment and significantly improved health-related QOL compared with placebo in all domains, including both mental and physical health. Interestingly, we did not observe a relationship between change in mental health–related QOL with magnitude of weight or HbA1c change,” the study authors stated. “This suggests the positive association with mental health benefits may not be entirely mediated by weight loss, which is known to independently improve QOL in obesity, or glycemic control.”
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