New data provide 'much-needed reassurance' that GLP-1s do not increase suicidality risk

Key takeaways:

• An active comparator, new user cohort study added to the growing body of evidence indicating GLP-1s do not affect suicidality.
• Experts discussed what this means and where future research should go.

The increasingly popular obesity and diabetes drugs known as glucagon-like peptide-1 receptor agonists do not seem to worsen suicidality despite previous concerns, according to recent data published in BMJ.

Case reports that linked GLP-1s to suicidality have raised regulatory concerns and left many wondering if these medications are harming the patients they intend to help, Laurent Azoulay, PhD, a professor and William Dawson Scholar at McGill University and a senior investigator at the Jewish General Hospital’s Lady Davis Institute in Montreal, Canada, told Healio.

“This is an important question given the rising use of GLP-1 receptor agonists in patients with type 2 diabetes and obesity,” he said.

In early January 2024, the FDA investigated several of these medications — Ozempic (semaglutide, Novo Nordisk), Wegovy (semaglutide, Novo Nordisk), Saxenda (liraglutide, Novo Nordisk) and two versions of the GIP/GLP-1 dual agonist tirzepatide — for suicidal ideation concerns. Shortly after, the FDA announced that preliminary results from their investigation found no evidence of the risk, but it could not be ruled out entirely.

Other research has found that GLP-1 receptor agonists did not increase suicide risk and that semaglutide may be linked to lower suicidal ideation risk than other obesity or diabetes drugs. One study even suggested GLP-1s may even lower some users’ suicidal ideation risk.

Because GLP-1s affect the brain, “it is crucial to rigorously investigate any potential link to suicidal thoughts,” according to Katherine Pannel, DO, FAPA, a psychiatrist and medical director for Right Track Medical Group in Oxford, Mississippi, and a member of the American Osteopathic Association.

“GLP-1 medications have been shown to reduce ‘food noise,’ the intrusive thoughts about food that many people experience throughout the day,” she said. “For individuals struggling with eating disorders like binge eating, this has been a game changer.”

The new data

In the active comparator, new user cohort study, Azoulay and colleagues found no increase in suicidality risk when comparing GLP-1 receptor agonists with two other commonly prescribed drug classes (dipeptidyl peptidase-IV [DPP-IV] inhibitors and sodium glucose cotransporter 2 inhibitors).

“This was also true when evaluating suicidal ideation, self-harm and suicide individually,” he said.

They evaluated cohorts of 36,082 patients with type 2 diabetes using GLP-1 receptor agonists and 234,028 DPP-4 inhibitor users.

The results “provide much-needed reassurance regarding the psychiatric safety of these drugs and contribute to recent studies that also found no link to suicidality,” Azoulay said. “This is particularly significant, as we know that these drugs affect the brain, which is likely beneficial; hence, the absence of an association implies that they are unlikely to have any harmful effects.”

There is a consistent “strong connection between obesity, diabetes and an increased risk of depression and poor mental health outcomes,” Pannel said.

“That link has been strongly established, making it especially encouraging to have another tool to use to help patients struggling with these conditions,” she told Healio. “This particular study is unique because it specifically examined patients taking GLP-1s who are at high risk of suicidality — a population that previous research on GLP-1s has largely excluded.”

In a related editorial, Peter Ueda, MD, PhD, an assistant professor at Karolinska Institutet in Sweden, and Björn Pasternak, MD, PhD, an associate professor and principal researcher at the same institution, applauded the carefully conducted study but also noted some limitations, including that less than 10% of the patients in the study used semaglutide, the most popular GLP-1 receptor agonist.

“Future studies may specifically assess the safety of semaglutide and tirzepatide, which have surpassed other GLP-1 receptor agonists in popularity owing to their larger effects on weight reduction and glucose control,” they wrote.

What’s next?

With so many questioning the impact of GLP-1s on health beyond just obesity and diabetes, Azoulay and Pannel said future research will be vital.

“GLP-1 receptor agonists have been on the market for nearly 2 decades, and we are starting to have a clearer picture of their effects in the real-world setting,” Azoulay said. “However, as newer, more powerful drugs enter the market, it will be essential to continue assessing their potential benefits and safety.”

Additional research would be prudent, according to Pannel, who hopes that further studies “will explore the mechanisms behind the reduction in ‘food noise.’” She anticipates that this line of study could result in more effective treatments for those with restrictive-type eating disorders.”

“The future of GLP-1s in mental health care is promising, especially in treating eating disorders, improving obesity-related mental health and potentially addressing mood disorders and neurodegenerative diseases such as Alzheimer’s disease,” Pannel said. “Ongoing research will be crucial in determining the full scope of their applications, but I am excited to see the potential positive role they may play in mental health care.”

References:

• Azoulay L, et al. BMJ. 2025;doi:10.1136/bmj-2024-080679.
• Ueda P, et al. BMJ. 2025;doi:10.1136/bmj.r351.