Study suggests no suicide signals in teens prescribed GLP-1 agonists

A retrospective cohort study suggests that treatment with a GLP-1 receptor agonist is associated with a lower risk of suicidal ideation and attempts in obese adolescents compared with patients treated with lifestyle interventions.

In over 6,900 obese adolescents, treatment with GLP-1 drugs was associated with lower rates of suicidal ideation or suicide attempts at 1-year follow-up compared to control subjects who received lifestyle interventions without GLP-1 treatment. It was associated with a 33% reduction in risk (versus 1.45% with treatment with GLP-1 drugs). 2.26%, HR 0.67, 95% CI 0.47-0.95, P=0.02), reported Liya Kerem, MD, MSc, and Joshua Stoker, MD, of the Hebrew University of Jerusalem.

Signs of an increase in suicidal ideation and attempts associated with GLP-1 use were found across subgroups stratified by gender, race, ethnicity, GLP-1 type, and diabetes status, and in 2019. was not seen over various follow-up periods. Three years, they note. JAMA Pediatrics.

These findings are “encouraging,” Kerem said. Today's Medpage, We noted that this is the first large-scale study to specifically examine this association among obese youth.

The study “provides new data to the existing literature where there was previously no evidence regarding the psychiatric safety profile of GLP-1 receptor agonists in this age group,” she said. “Although our results do not prove causation, the finding that the risk of suicidal behavior was reduced may alleviate some of the concerns stemming from individual case reports of increased suicidality. there is.”

Following the case reports in question, the FDA and the European Medicines Agency (EMA) launched an investigation into the safety of this drug class used for type 2 diabetes, obesity, or both. Currently, GLP-1 drugs indicated for obese patients over 12 years of age include: Liraglutide (Saxenda) and Semaglutide (Wegovy).

FDA found no evidence to support a causal relationship between GLP-1 agonists and suicidality and self-harm. Preliminary evaluation. Similarly, EMA no evidence found A nine-month independent review confirms the cause-and-effect relationship. Since then, more studies (all in adult patients) have also investigated this issue. some found an association and others didn't.

Per current FDA guidance, GLP-1 drugs should be avoided in people with a history of suicide attempts or active suicidal thoughts. The agency also advised clinicians to monitor patients taking these drugs for new or worsening depression, suicidal thoughts, or unusual changes in mood or behavior.

“It should be emphasized that we cannot infer causality from our observational study design, and further research is needed to validate these findings and investigate the underlying mechanisms that may contribute to the association. It is necessary,” Kerem said. “Clinical decisions should always be made on an individualized basis, taking into account each patient's unique circumstances.”

In their study, Kerem and Stoker used electronic medical records from the TriNetX global federated network, which features data from 120 medical institutions, primarily based in the United States, from December 2019 to June 2024. I did. A total of 4,052 youth were identified in the GLP-1 cohort with obesity and anti-obesity interventions, and 50,112 in the lifestyle intervention without GLP-1 therapy cohort. Suicidal ideation and attempts were identified using ICD-10 codes from health records.

Propensity score matching was used to balance groups with respect to several characteristics, including demographics, psychiatric medication use, psychiatric comorbidities, and diagnoses related to socioeconomic status and healthcare access. This resulted in 3,456 participants in each balanced cohort.

Before propensity score matching, GLP-1 users were older (15.5 years vs. 14.7 years), more likely to be female (59% vs. 49%), had a higher BMI (41.9 vs. 33.8), and were more likely to have The rate was high. Prevalence of diabetes (40% vs. 4%). They were also more likely to have a history of psychiatric diagnosis (17% vs. 9% for mood disorders) and history of psychiatric medication use (18% vs. 7% for antidepressants). Ta.

Dr. Kerem noted that this suggests that GLP-1 receptor agonists “should not be categorically avoided in adolescents with co-occurring obesity and mental illness.” This is because treatment is not likely to increase risk in this situation.

As expected for this drug class, the incidence of gastrointestinal symptoms was significantly higher among youth prescribed GLP-1 agents (6.9% vs 5.4%; HR 1.41, 95% CI 1.12-1.78, P=0.003). There was no difference in the incidence of upper respiratory tract infections between groups.

In an alternative analysis starting 1 year before the index event, researchers found no significant difference in the incidence of suicidal ideation or attempts between groups (HR 0.93, 95% CI 0.55-1.57, P=0.79), “provides further validation that the observed differences are more likely due to GLP-1 receptor agonist initiation than to a pre-existing condition.”

Researchers said suicide rates were likely underestimated because they relied on ICD codes that reflected only those who sought treatment or disclosed suicidal tendencies to a clinician. Ta. However, this restriction “applies equally to both the study and control groups.”

“It would be valuable for future studies to include studies that directly examine psychiatric outcomes as a primary endpoint,” Kerem said. “Additionally, exploring the biological pathways by which GLP may have potential psychiatric effects may further clarify its role in this patient population.”

If you or someone you know is considering suicide, call or text 988 or 988 Suicide and Crisis Lifeline Website.