GLP-1 Drugs May Lower Suicide and Depression Risk in Children and Teens With Obesity or Diabetes | Research

The takeaway

In a study of over 2,000 children and adolescents, GLP-1 receptor agonist use was associated with 89% lower risk of suicidal ideation/behaviors and 63% lower risk of depression compared to metformin, with no effect on anxiety.

89% lower suicidal ideation risk
Children and adolescents using GLP-1 receptor agonists had dramatically lower rates of suicidal thoughts and behaviors compared to metformin users (HR 0.11)

What the researchers found

Among approximately 2,000 children and adolescents (mean age ~14.2 years, ~61% female) with up to 4 years of follow-up:

- Suicidal ideation/behaviors: GLP-1 RA users had significantly lower risk (HR 0.11, 95% CI 0.02-0.86; risk difference -10.45 per 1,000 person-years)

- Depression: GLP-1 RA users had significantly lower risk (HR 0.37, 95% CI 0.17-0.78; risk difference -25.64 per 1,000 person-years)

- Anxiety: No significant difference (HR 1.13, 95% CI 0.69-1.84; risk difference 5.95 per 1,000 person-years)

All comparisons were against prevalent metformin users.

Why it matters

With GLP-1 drugs increasingly prescribed to children and teens for obesity, the European Medicines Agency and FDA have flagged concerns about potential suicide risk. This study provides the first large pediatric-specific evidence and finds the opposite — these drugs may actually be protective for mental health. This is critical information for parents, pediatricians, and regulators making prescribing decisions.

How the study worked

Retrospective cohort study using the OneFlorida+ electronic health records database (January 2020 to January 2024). The study used a prevalent-new user design with target trial emulation framework and stabilized inverse probability of treatment weighting (sIPTW) for confounding control. Weighted Cox proportional hazards models assessed the risk of suicidal ideation/behaviors, depression, and anxiety in children and adolescents (age 6-17) starting GLP-1 RAs compared to prevalent metformin users.

What this study cannot tell us

This is a retrospective observational study (preprint, not yet peer-reviewed), so it cannot establish causation. The comparison with metformin users may introduce selection bias. The confidence interval for suicidal ideation/behaviors was wide (HR 0.02-0.86), reflecting small event numbers. The anxiety finding showed a non-significant upward trend that warrants monitoring. Confounding by indication (more depressed patients might not be prescribed GLP-1 RAs) cannot be fully excluded despite weighting.

How to read the evidence

This is a well-designed retrospective cohort study using target trial emulation methodology and rigorous confounding controls. However, it is a preprint (not yet peer-reviewed), observational in nature, and based on EHR data which may have coding limitations. The wide confidence intervals for some outcomes reflect limited event numbers.

When this study was published

Published as a preprint in 2025, this is among the first studies to specifically examine GLP-1 RA mental health safety in the pediatric population — a critical gap in current evidence.

The bigger picture

This study directly addresses one of the most sensitive safety questions surrounding GLP-1 drugs. As pediatric obesity reaches epidemic levels and GLP-1 prescriptions surge in young people, understanding mental health implications is crucial. The finding that these drugs may reduce rather than increase suicide risk and depression could reshape the risk-benefit discussion for pediatric prescribing and inform regulatory guidance.

Questions still open

What mechanisms might explain GLP-1 RA's apparent protective effect against depression and suicidal ideation in youth?
Does the weight loss and metabolic improvement from GLP-1 drugs drive the mental health benefits, or are there direct neurological effects?
Should the non-significant upward trend in anxiety with GLP-1 RA use be monitored more closely in larger studies?

Common questions

Should parents worry about mental health side effects of GLP-1 drugs in their children?

This study suggests the opposite of what was feared — children and teens on GLP-1 drugs actually had lower rates of depression and suicidal thoughts compared to those on metformin. However, this is one study and a preprint, so it should be interpreted with caution. The slight (non-significant) increase in anxiety warrants watching. Parents should discuss mental health monitoring with their child's doctor regardless of medication.

Why might GLP-1 drugs reduce depression and suicide risk in young people?

Several mechanisms could explain this. Weight loss and improved metabolic health may boost self-esteem and reduce the psychological burden of obesity in teenagers. GLP-1 receptors are also found in brain regions involved in mood regulation, suggesting possible direct neurological effects. Additionally, better diabetes control may reduce the psychological distress associated with managing a chronic disease. More research is needed to determine which factors are most important.

Read the original research

Risk of Suicidal Ideation and Behaviors, Depression, and Anxiety with GLP-1 Receptor Agonist Use in Children and Adolescents: A Target Trial Emulation Study.

medRxiv : the preprint server for health sciences

View on PubMed ↗Publisher’s paper ↗

Citation

Kotecha, Pareeta; Lee, Yao An; Bernier, Angelina V; Westen, Sarah C; Smith, Steven M; Zhang, Pengyue; Hannon, Tamara S; Bian, Jiang; Guo, Jingchuan. (2025). Risk of Suicidal Ideation and Behaviors, Depression, and Anxiety with GLP-1 Receptor Agonist Use in Children and Adolescents: A Target Trial Emulation Study.. medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2025.11.11.25339931