FDA finds no evidence GLP-1s cause suicidal thoughts

The U.S. Food and Drug Administration said on January 11, 2024, that its preliminary evaluation of reports of suicidal thoughts or actions in patients taking GLP-1 receptor agonists "has not found evidence that use of these medicines causes suicidal thoughts or actions" ^[1]. The agency said it would keep investigating because the number of such events was small in both treated patients and comparison groups ^[1].

The drugs covered by the review include semaglutide (Ozempic, Rybelsus, Wegovy), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), exenatide (Byetta, Bydureon BCise), lixisenatide (Adlyxin) and the combination products Xultophy and Soliqua, as well as tirzepatide (Mounjaro, Zepbound), which the FDA notes is a dual GIP and GLP-1 receptor agonist ^[1]. The FDA approved the first drug in the class in 2005 ^[1].

What the FDA reviewed

Over several months, FDA staff conducted detailed reviews of reports of suicidal thoughts or actions submitted to the FDA Adverse Event Reporting System, known as FAERS ^[1]. The agency said the information in those reports was "often limited" and that these events can be influenced by other factors, so the reports "did not demonstrate a clear relationship" with GLP-1 use ^[1].

The agency also looked at clinical trials, including large outcome studies, and at observational studies. Those reviews did not find an association between the drugs and suicidal thoughts or actions either ^[1]. But the FDA was explicit about the limits of that finding: "because of the small number of suicidal thoughts or actions observed in both people using GLP-1 RAs and in the comparative control groups, we cannot definitively rule out that a small risk may exist" ^[1].

The concern did not come out of nowhere. In July 2023 the European Medicines Agency said it was examining similar reports, and in September 2023 Reuters reported that the FDA would also assess the issue, citing 265 reports of suicidal ideation linked to GLP-1 medicines ^[2].

Separate research published around the same time pointed in the same direction as the FDA's preliminary read. A study in Nature Medicine looked at electronic health records from 240,618 patients with overweight or obesity who were prescribed semaglutide or a non-GLP-1 weight-loss medicine. Compared with the other drugs, semaglutide was linked to a lower risk of first-time and recurrent suicidal ideation (hazard ratios of 0.27 and 0.44) ^[2]. One of the authors, Nora Volkow, MD, director of the National Institute on Drug Abuse, cautioned that "our study does not indicate that taking semaglutide could reduce risk of suicidal ideations or that it actively protects against suicidal ideations—such a conclusion would require clinical trials" ^[2].

A. Michael Lincoff, MD, of the Cleveland Clinic, co-chair of the steering committee for the SELECT cardiovascular outcomes trial of semaglutide, told TCTMD that trial did not show an increase in psychiatric adverse events, though results were not broken down by suicidal ideation specifically. "I am unaware of any compelling evidence of an increased risk with GLP-1s," he said ^[2].

Why it matters for patients

The FDA's statement does not change what is printed on the labels. Prescribing information for GLP-1 drugs approved for obesity or overweight still contains information about the risk of suicidal thoughts and actions ^[1]. The FDA said that warning language is also in the labels of other weight-loss medicines and is based on events seen with a variety of older drugs used or tested for weight loss — not on new findings specific to this class ^[1].

The agency told patients not to stop taking a GLP-1 without first talking to a health care professional, because stopping may worsen the underlying condition, and to report new or worsening depression, suicidal thoughts, or unusual changes in mood or behavior ^[1]. Clinicians were told to monitor for those changes, consistent with existing prescribing information ^[1]. The FDA pointed to the 988 Suicide and Crisis Lifeline, available by call or text 24 hours a day ^[1].

What is not yet known is whether a small risk exists that these analyses were too underpowered to detect. The FDA said it could not rule that out ^[1].

What happens next

The FDA said further work would include a meta-analysis combining clinical trial data across all GLP-1 products and an analysis of postmarketing data through the Sentinel System, a large network of health insurance claims and patient health records used to investigate safety questions ^[1]. The agency said it would share final conclusions and recommendations after completing that review ^[1].

The FDA's page on this 2024 communication now carries a link to a later drug safety communication, dated January 13, 2026, in which the agency requests removal of the suicidal behavior and ideation warning from GLP-1 medications ^[1].