A recent study published in JAMA Pediatrics indicates that GLP-1 receptor agonists may decrease the risk of suicidal ideation and suicide attempts in adolescents with obesity. The research, which analyzed data from over 54,000 adolescents, found that those treated with GLP-1 drugs had a 33% reduction in suicidal thoughts compared to those who received lifestyle interventions alone. This finding addresses concerns about potential psychiatric risks associated with GLP-1 medications in this age group.
The study, led by Dr. Liya Kerem from Hadassah Hebrew University Medical Center, Jerusalem, aimed to evaluate the impact of GLP-1 receptor agonists on psychiatric outcomes in adolescents with obesity. "Given that obesity in adolescence is already associated with an increased risk of depression and suicidal ideation, and considering the rise in GLP-1 receptor agonist prescriptions since FDA approval in 2020, it was crucial to investigate whether this treatment impacts psychiatric outcomes," Dr. Kerem explained.
Study Design and Key Findings
The researchers utilized data from the TriNetX health record database, examining adolescents aged 12 to 18 diagnosed with obesity between December 2019 and June 2024. The study compared 4,052 adolescents prescribed GLP-1 receptor agonists—specifically liraglutide (Saxenda, Novo Nordisk) or semaglutide (Wegovy, Novo Nordisk)—with 50,112 adolescents treated with lifestyle intervention alone. Suicidal ideation and suicide attempts were tracked for up to one year after the initiation of either treatment.
After propensity-score matching, the study included 3,456 adolescents in each group (GLP-1 users vs. lifestyle intervention), with a mean age of approximately 15.5 years and roughly 60% female participants in both cohorts. The incidence rate of suicidal ideation or attempts was significantly lower in the GLP-1 group (1.45%) compared to the lifestyle intervention group (2.26%), with a hazard ratio of 0.67 (95% CI, 0.47-0.95; P = .02).
Adverse Events and Tolerability
While the GLP-1 group experienced a higher incidence of gastrointestinal symptoms (6.9% vs. 5.4%; HR = 1.41; 95% CI, 1.12-1.78; P = .003), they had a significantly lower risk of acute pancreatitis (0.29% vs. 0.67%; HR = 0.41; 95% CI, 0.19-0.88; P = .02). There was no significant difference in the risk of upper respiratory tract infections between the two groups.
Implications and Future Research
The findings suggest that GLP-1 receptor agonists do not increase the risk of suicidality in adolescents with obesity and may even offer a protective effect. "While individual cases of increased suicidality following GLP-1 receptor agonist use have been reported, our large cohort study found no such association and instead suggested a decreased risk of suicidal behavior in adolescents receiving this treatment," Dr. Kerem noted.
The researchers emphasize the need for future studies to explore the underlying mechanisms through which GLP-1 receptor agonists may influence psychiatric outcomes. Potential mechanisms include the impact of weight loss on mood and the direct effects of GLP-1 medications on brain chemistry.
Current Treatment Landscape
With childhood obesity rates rising—affecting approximately 1 in 5 U.S. children—GLP-1 medications are increasingly being prescribed to adolescents. This study provides crucial data for clinicians weighing the benefits and risks of these medications in this population. The results indicate that, contrary to some concerns, GLP-1 therapy may be associated with improved mental health outcomes in adolescents with obesity.
