FDA Requests Removal of Suicidal Ideation and Behavior Warning From GLP-1 RA Therapies

The US Food and Drug Administration (FDA) has requested the removal of information regarding the risk of suicidal ideation and behavior (SI/B) from the labeling of glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications that currently include such language.1

As described in a January 13, 2026, release from the Agency, affected products include liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound). The action follows a comprehensive FDA review that found no increased risk of SI/B associated with the use of GLP-1 RA medications.1

Liraglutide, semaglutide, and tirzepatide are each approved for weight reduction in individuals with obesity or overweight. At the time of their original FDA approvals, the labeling for each of these products included information in the Warnings and Precautions section about the potential risk of SI/B. Of note, similar information about SI/B is also included in the labeling of other types of weight loss medicines and is based on reports of such events observed with a variety of older medicines used or studied for weight loss.1

Labeling for GLP-1 RA medications that are approved to improve glycemic (blood sugar) control or other complications in patients with type 2 diabetes mellitus does not currently include information on the risk of SI/B.1

The FDA approved the first GLP-1 receptor agonist in 2005 as adjunctive therapy to improve glycemic control in type 2 diabetes, a milestone that has since reshaped multiple areas of medicine. What began as a diabetes therapy has rapidly evolved into one of the most influential drug classes in modern clinical practice, with expanding indications across endocrinology, cardiology, nephrology, and hepatology. Today, several GLP-1 receptor agonists are available, and their transformative clinical impact, coupled with unprecedented patient and provider demand, has driven sustained nationwide shortages from 2023-2025, underscoring their central role in contemporary care.1

In July 2023, after receiving postmarketing reports of SI/B in patients taking GLP-1 RA medications, the FDA initiated further investigation of the potential risk of SI/B for GLP-1 RA medications. Findings from a preliminary review of clinical trial and postmarketing data, including observational studies and case reports, were publicly reported by the FDA in its January 2024 Drug Safety Communication.1,2

The initial review of GLP-1 RA clinical trial data did not find an association between the use of GLP-1 RAs and the occurrence of SI/B. However, because of the small number of cases of SI/B observed in individual trials, the Agency cited considerable uncertainty in the risk estimate.1

To address this concern, the FDA performed a comprehensive meta-analysis of clinical trials across GLP-1 RA drug development programs to improve the precision of the risk estimate. The meta-analysis assessed the risk of SI/B comparing GLP-1 RA medications to placebo in 91 placebo-controlled GLP-1 RA medication trials enrolling 107,910 patients, including 60,338 treated with a GLP-1 RA and 47,572 treated with placebo. Of note, results did not show an increased risk for SI/B or for other relevant psychiatric adverse events such as anxiety, depression, irritability, or psychosis.1

The FDA additionally conducted a retrospective cohort study using administrative healthcare claims data from the FDA Sentinel System to compare the risk of intentional self-harm between new users of GLP-1 RAs and sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus. The study population included 2,243,138 users (1,161,983 initiated on a GLP-1 RA and 1,081,155 initiated on a SGLT2i) from 10 data partners between October 2015 and September 2023.1

After controlling for baseline confounders in the study, the FDA did not find an increased risk of intentional self-harm in GLP-1 RA users compared to SGLT2i users. Similarly, the FDA did not find an increased risk in the subgroup of patients with both type 2 diabetes mellitus and obesity.1

The FDA also reviewed published observational and pooled studies evaluating the relationship between GLP-1 RAs and SI/B, and related outcomes. The Agency’s review concluded that the totality of these studies does not support a causal relationship between the use of GLP-1 RAs and the occurrence of SI/B.1

Consistent with these findings, the Agency is requesting that application holders remove information regarding the risk of SI/B from the labeling of GLP-1 RA medications that currently include such language.1

References

1. US Food and Drug Administration. FDA Requests Removal of Suicidal Behavior and Ideation Warning from Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications. January 13, 2026. Accessed January 13, 2026. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-suicidal-behavior-and-ideation-warning-glucagon-peptide-1-receptor-agonist-glp?utm_medium=email&utm_source=govdelivery

2. US Food and Drug Administration.Update on FDA’s ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity. January 11, 2024. Accessed January 13, 2026. https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type