GLP1R medications show promise in reducing suicidal ideation among adolescents with obesity

A new study reveals that GLP1R medications not only aid in weight loss for adolescents with obesity but may also significantly lower the risk of suicidal thoughts and behaviors, offering hope for improved mental health outcomes.

Study: Risk of Suicidal Ideation or Attempts in Adolescents With Obesity Treated With GLP1 Receptor Agonists. Image Credit: SeventyFour/Shutterstock.com

In a recent study published in JAMA Pediatrics, researchers examined the links between the use of certain medications used to treat obesity in adolescents and their likelihood of suicidal thoughts or attempts.

The findings indicate that adolescents who are prescribed glucagon-like peptide 1 receptor agonists (GLP1R) to treat obesity showed lower rates of suicidal thoughts and attempts than those prescribed lifestyle interventions, suggesting that the medication has psychiatric benefits.

Background

Estimates suggest that childhood obesity affects more than 124 million children and adolescents globally, increasing eight-fold among children between 5 and 19 in the past four decades.

More than half of children could have obesity by 35 if current trends continue, and the recent pandemic worsened outcomes for adolescents diagnosed with obesity.

Childhood obesity has been implicated in several health issues in the immediate and long term, including liver disease, type 2 diabetes, heart disease, and premature death. Genetic factors associated with appetite regulation are an important factor for obesity development.

Treating this condition is challenging, as lifestyle changes alone can have limited success. GLP1R medications have shown effectiveness in weight reduction and metabolism improvement in adolescents, but their psychiatric effects have not been well documented.

In adults, there is some evidence that adults who use GLP1R are at a lower risk of suicidal ideation than people on other drugs for weight loss.

About the study

As GLP1R use in adolescents increases and given the mental health risks associated with pediatric obesity, researchers investigated the link between GLP1R and suicidality in adolescents with obesity using data from a healthcare network.

They used a retrospective cohort design, including American adolescents between 12 and 18 diagnosed with obesity and prescribed either semaglutide or liraglutide, both GLP1R drugs.

Adolescents using GLP1R medication were compared to a control group of adolescents undergoing behavioral or lifestyle interventions to manage obesity, such as exercise or diet.

This was done through a matching method where each adolescent using a GLP1R medication was matched to one in the control group who was most similar in terms of psychiatric history, race, sex, and age.

The measured outcome was the incidence of suicidal thoughts or attempts during the follow-up period of 12 months.

Findings

The initial sample comprised 77,854 adolescents diagnosed with obesity; after exclusions, 4,052 individuals were in the group taking GLP1R medication, while 50,112 were in the control group. After matching, 3,456 patients from each cohort were included.

Before matching, adolescents taking GLP1R were older (15.5 compared to 14.7) and more likely to be female (59% compared to 49%) than those in the control group.

They also reported a higher body mass index (BMI), were more likely to have been diagnosed with diabetes (40% compared to 4%) and were more likely to have been given a psychiatric diagnosis (17% compared to 9%) and use antidepressants (18% compared to 7%).

After matching these characteristics, adolescents taking GLP1R had a 33% lower risk of suicidal ideation or attempts than those in the control group.

They also experienced more gastrointestinal symptoms but had fewer cases of acute pancreatitis. The study showed no significant difference in upper respiratory infection incidence between the groups.

Researchers also identified additional prescriptions, finding that 69% of adolescents taking GLP1R medication received at least one additional GLP1R prescription during the follow-up period.

They were more likely to be prescribed phentermine, another appetite suppressant, while those in the control group were more likely to be prescribed bariatric surgery.

Conclusions

The study examined 6,912 adolescents with obesity and assessed their risk of suicidal ideation and attempts, comparing those prescribed GLP1R medication with those who were not. Semaglutide showed fewer psychiatric adverse effects and improved weight-related quality of life compared to liraglutide or a placebo.

They found a lower risk of these outcomes in the former group, but adolescents given GLP1R also experienced more gastrointestinal symptoms, which are common side effects of the medication.

These findings add to the evidence of the psychiatric effects of obesity medication. A previous clinical trial had found that a GLP1R medication significantly reduced BMI but reported three suicide-related events that were thought to be unrelated to the drug.

This led regulatory bodies to approve the drug but recommend that suicidal thoughts and depression be carefully monitored.

While these results are indicative, the observation design and retrospective nature limit researchers’ abilities to draw causal inferences, opening avenues for further research.

As obesity during adolescence comes with significant mental health challenges and can lower quality of life, such research could be very beneficial.