GLP-1 receptor agonist use and risk of suicide death

JAMA Internal Medicine

About The Study: 

This cohort study, including mostly patients with type 2 diabetes, does not show an association between use of glucagon-like peptide-1 (GLP-1) receptor agonists and an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders.

Corresponding Author: To contact the corresponding author, Peter Ueda, MD, PhD, email peter.ueda@ki.se.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2024.4369)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2024.4369?guestAccessKey=2dc15077-db5b-45cf-b2f1-f1fcf6020c5c&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=090324

 

---

Journal

JAMA Internal Medicine

No link found between popular diabetes medication and suicide

Karolinska Institutet

 

image: 

Peter Ueda

view more 

Credit: Stefan Zimmerman

There has been concern that common diabetes drugs could increase the risk of suicide and self-harm. In a new study, led by researchers at Karolinska Institutet and published in Jama Internal Medicine, no such risk increase was observed.

Drugs of the type GLP-1 analogues lower blood sugar levels and are used by millions of people worldwide. They are mainly used to treat diabetes, but drugs such as Ozempic have also been shown to be effective against obesity, which has increased their popularity.

At the same time, both American and European drug authorities have warned that there may be risks associated with the drugs.

Last year, the European Medicines Agency (EMA) launched an investigation following around 150 reported possible cases of suicidal thoughts and self-injury with use of GLP-1 analogues.

The investigation was completed in the spring and based on the limited data available at the time, it concluded that there were no obvious connections. Researchers at Karolinska Institutet can now further support this conclusion. They have analyzed large amounts of data from people treated with GLP-1 analogues in Sweden and Denmark .

"We found no clear link between the use of the drugs and an increased risk of suicide death, self-harm or depression and anxiety-related disorders. This is reassuring." says Björn Pasternak, principal researcher at the Department of Medicine, Solna, Karolinska Institutet, and one of the study's lead authors.

The data includes approximately 300,000 adults aged 18–84 who started treatment with either GLP-1 analogues or SGLT2 inhibitors, another type of diabetes medication, during the years 2013–2021.

After a mean follow-up period of just over two years, there was no apparent increase in the proportion of people who committed suicide, engaged in self-harm, or suffered from depression or anxiety-related disorders among users of GLP-1 receptor agonists.

Peter Ueda, assistant professor at the same department and one of the study's main authors, nevertheless emphasizes the importance of larger studies as more data is collected.

"It is important to specifically examine people with previous self-harm or suicidal thoughts as they are at increased risk and it is possible that the drug’s safety profile differs in this group," he says. 

The study was conducted in collaboration with researchers in Denmark and mainly funded by Karolinska Institutet. Some of the researchers report conflicts of interest, see the study for more information.

Publication: "GLP-1 receptor agonists and risk of suicide death: nationwide cohort study in Sweden and Denmark", Peter Ueda, Jonas Söderling, Viktor Wintzell, Henrik Svanström, Laura Pazzagli, Björn Eliasson, Mads Melbye, Anders Hviid, Björn Pasternak. JAMA Internal Medicine, online September 3, 2024. 

---

Journal

JAMA Internal Medicine

Method of Research

Observational study

Subject of Research

People

Article Title

GLP-1 receptor agonists and risk of suicide death: nationwide cohort study in Sweden and Denmark

Article Publication Date

3-Sep-2024

Penn study finds taking semaglutide for weight management does not increase risk of depression or suicidal behavior in people without known major psychopathology

Analysis of over 3,500 participants in clinical trials finds no increased risk of mental health issues among those using the weight loss medication

University of Pennsylvania School of Medicine

PHILADELPHIA— Taking the weight loss medication semaglutide did not increase the risk of depressive symptoms, suicidal thoughts, or suicidal behavior in persons without known major mental health disorders, according to a new study led by researchers from the Perelman School of Medicine at the University of Pennsylvania published this week in JAMA Internal Medicine. Both the Food and Drug Administration (FDA) and the European Medicines Agency are actively monitoring the psychiatric safety of semaglutide and similar medications after post marketing surveillance reports of depression, suicidal thoughts (ideation), and suicidal behavior in patients taking the drugs for the management of type 2 diabetes or obesity.

Semaglutide has emerged as a significant advancement in the field of weight management. Initially developed as a treatment for type 2 diabetes, the drug gained widespread attention after clinical trials showed it reduced baseline body weight by approximately 10%-15%. Weekly injectable medications like semaglutide have become a popular option for healthcare providers to prescribe for patients. As many as 5 million Americans were prescribed semaglutide in 2023, with nearly four in ten taking it for weight management.

The new study, led by Thomas Wadden, PhD, a professor of Psychology in Psychiatry and the former director of Penn’s Center for Weight and Eating Disorders, analyzed data from over 3,500 participants across four major clinical trials. Researchers examined data from the Semaglutide Treatment Effect in People with obesity (STEP) trials – STEP 1, 2, 3, and 5. These studies were crucial in gaining approval from the FDA to use semaglutide 2.4 mg for obesity.

"The STEP trials provide strong evidence that semaglutide 2.4 mg reduces body weight and improves numerous health complications associated with obesity. Our new analyses provide assurance that the medication, when taken by individuals who are free of significant mental health concerns, does not increase the risk of depression, suicidal thoughts, or suicidal behavior,” Wadden said. He noted, however, that further study is needed of the psychiatric safety of semaglutide 2.4 mg when used by persons with current major depressive disorder, other serious mental illness (such as schizophrenia), or a history of suicide attempt. Individuals with such conditions were not included in the STEP trials.

The study examined changes in depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9) and assessed suicidal ideation and behavior using the Columbia Suicide Severity Rating Scale. Across the 68-week STEP 1-3 trials, semaglutide-treated participants, as compared to those who received placebo, did not show an increased risk of developing moderately severe symptoms of depression or of suicidal thoughts or behavior. Similar findings were observed in the 104-week STEP 5 study.

Examining all four STEP trials, researchers found that 1% or fewer of participants reported suicidal ideation or behavior during treatment, with no differences between semaglutide 2.4 mg and placebo. Moreover, only 2.8% of the semaglutide-treated participants, versus 4.1% of those who received placebo, reported levels of depression at some point during treatment that required evaluation by a mental health professional. These rates are consistent with the risk of significant depression in the general population. “It is certainly possible that individuals with overweight or obesity who take semaglutide may experience depressive symptoms or suicidal ideation or behavior, but the data suggest that persons not taking semaglutide – in the placebo group in this study - are equally likely to experience these conditions,” said Gregory Brown, PhD, a study co-author and Director of the Penn Center for the Prevention of Suicide at the Perelman School of Medicine. Wadden and Brown noted that their study’s findings for semaglutide are consistent with results of the FDA’s most recent analysis of post-marketing surveillance data for this class of medications which did not find “evidence that use of these medicines causes suicidal thoughts or actions." 

If you or a loved one are experiencing a suicidal crisis or emotional distress call the Suicide and Crisis Lifeline at 988.

The study was funded by Novo Nordisk.

Editor’s Note: Wadden has received grants from Novo Nordisk, as well as consulting fees from Novo Nordisk, advisory board service fees from Weight Watchers, and grant support from Eli Lilly.

###

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

 

---

Journal

JAMA Internal Medicine