GLP-1 Medications and Mood: What the FDA and Studies Say

By the Healthy Weight Loss 4 U Clinical Content Team · Published October 20, 2026 · Updated October 20, 2026 · 9 min read

Key takeaways

• FDA asked on January 13, 2026 for the suicidal behavior and ideation warning to be removed from Saxenda, Wegovy and Zepbound labels; the three labels now list it as removed ^[1][3][4][5].
• FDA's review pooled 91 placebo-controlled trials (107,910 patients) and found no increased risk of suicidal behavior or ideation or of related psychiatric events ^[1].
• A Sentinel claims analysis of 2,243,138 new users found no increased risk of intentional self-harm for GLP-1 receptor agonists compared with SGLT2 inhibitors ^[1].
• In Sweden and Denmark (124,517 GLP-1 users), suicide deaths were rare and the hazard ratio of 1.25 had a wide interval (0.83 to 1.88), so a small risk could not be excluded ^[11].
• FDA's advice did not change: tell a clinician about new or worsening depression or unusual mood changes, and call or text 988 for free 24/7 support if in distress ^[1][13].

What do the Wegovy, Zepbound and Saxenda labels say about suicidal thoughts today?

The current U.S. labels for all three weight-management products no longer contain a Suicidal Behavior and Ideation warning. The Wegovy label (revised 05/2026) lists "Suicidal Behavior and Ideation (5.10)" as removed in 01/2026 ^[3]. The Saxenda label (revised 02/2026) lists the same section as removed in 02/2026 ^[5]. The Zepbound label (revised 04/2026) lists it as removed in 02/2026 ^[4].

The change followed a request from the FDA. On January 13, 2026, the agency issued a Drug Safety Communication asking the holders of the Saxenda (liraglutide), Wegovy (semaglutide) and Zepbound (tirzepatide) applications to remove suicidal behavior and ideation information from labeling. FDA said its review "found no increased risk" and that the totality of the studies does not support a causal relationship ^[1].

FDA also noted that GLP-1 receptor agonist labels approved for type 2 diabetes never carried this information, while the three weight-loss labels did ^[1]. A label that no longer lists a warning is not a promise that no individual will ever have mood changes. It reflects FDA's reading of the available trial and claims data, which are described below ^[1].

This article describes what regulators and studies say. It is not medical advice, and a licensed clinician decides what is appropriate for a particular person after an evaluation.

What did the labels say before the warning was removed?

Before removal, the weight-management labels told prescribers to monitor for mood changes and to avoid the drug in people with a history of suicide attempts or active suicidal ideation. The Wegovy label revised 03/2024 stated that suicidal behavior and ideation "have been reported in clinical trials with other weight management products" and advised avoiding Wegovy in patients with a history of suicidal attempts or active suicidal ideation. It also told clinicians to monitor for new or worsening depression, suicidal thoughts or behavior, or unusual changes in mood or behavior, and to discontinue Wegovy in patients who develop suicidal thoughts or behaviors ^[6].

The Zepbound label revised 09/2025 used nearly identical wording in section 5.9, including the same monitoring, discontinuation and avoidance statements ^[7]. Neither section reported trial counts of suicidal events for the drug itself. The wording refers to reports from trials of other weight-management products ^[6][7].

Whether the GLP-1 drugs themselves raised risk was the question regulators studied from 2023 onward, as described next ^[1][2][8].

What did the FDA's reviews find?

FDA looked at the question twice, in January 2024 and again for its January 2026 decision, and neither review found evidence that these drugs cause suicidal thoughts or actions. The agency began evaluating after receiving reports starting in July 2023 ^[1].

In the January 11, 2024 preliminary evaluation, FDA reviewed FDA Adverse Event Reporting System (FAERS) reports, clinical trials, observational studies, a meta-analysis across GLP-1 products, and Sentinel System data. It found no evidence that the medicines cause suicidal thoughts or actions, but said it could not "definitively rule out that a small risk may exist," and it kept reviewing. FDA noted that FAERS reports often had limited information and that these events were rare in both GLP-1 users and control groups ^[2].

The January 13, 2026 communication reported the completed work. It included a meta-analysis of 91 placebo-controlled trials with 107,910 patients (60,338 on a GLP-1 receptor agonist and 47,572 on placebo), which found no increased risk of suicidal behavior or ideation or of related events such as anxiety, depression, irritability or psychosis. It also included a retrospective Sentinel cohort of 2,243,138 new users from October 2015 to September 2023 across 10 data partners (1,161,983 on a GLP-1 receptor agonist and 1,081,155 on an SGLT2 inhibitor). That analysis found no increased risk of intentional self-harm with GLP-1 receptor agonists, including in people with both type 2 diabetes and obesity ^[1].

What did the European Medicines Agency conclude?

Europe's safety committee reached a similar conclusion in April 2024. The European Medicines Agency (EMA) announced a review on July 11, 2023, after Iceland's medicines regulator reported cases of suicidal thoughts and self-harm. About 150 reports were retrieved for analysis. EMA said it was not clear whether the cases were linked to the medicines, and suicidal behavior was not listed as a side effect in EU product information for any GLP-1 receptor agonist at that time ^[8].

At its April 8 to 11, 2024 meeting, the Pharmacovigilance Risk Assessment Committee (PRAC) concluded that the evidence "does not support a causal association" between GLP-1 receptor agonists and suicidal and self-injurious thoughts and actions, and that no update to the product information was warranted. The conclusion covered dulaglutide, exenatide, liraglutide, lixisenatide and semaglutide. PRAC drew on non-clinical studies, clinical trials, post-marketing data and two electronic health record studies in people with type 2 diabetes or overweight ^[9].

FDA and EMA are separate regulators, and each reached its own conclusion on the question ^[1][9].

What do large observational studies show?

Three published cohort studies found no higher risk, but they differ in design, drug and certainty. The table summarizes what each reported, and all three are observational, so they can show association but not prove cause.

The Nature Medicine study compared propensity-score-matched groups in a cohort with a mean age of 50.1 years that was 72.6% female. Results were consistent across sex, age and ethnicity groups. A replication in 1,589,855 patients with type 2 diabetes reported similar findings, and the authors concluded that their results do not support higher suicidal ideation risk with semaglutide ^[10].

The Nordic study is the most cautious of the three. Its point estimate for suicide death, 0.23 vs 0.18 per 1,000 person-years, was slightly higher in GLP-1 users, but the interval was wide enough to include no difference. The authors said the upper limit corresponds to an absolute increase of no more than 0.16 events per 1,000 person-years ^[11]. Combined suicide death or nonfatal self-harm was lower in the GLP-1 group, and incident depression or anxiety-related disorders did not differ (HR 1.01, 95% CI 0.97 to 1.06) ^[11].

What does FDA tell patients and clinicians to do?

In 2026, FDA told patients and caregivers to continue taking the medication as prescribed, to discuss any concerns with a health care professional, and to report side effects to its MedWatch program ^[1]. In 2024 it likewise advised against stopping a GLP-1 medicine without first speaking with a health care professional, since stopping may worsen the condition being treated ^[2]. These are general instructions, and the decision about any one person's treatment belongs to that person's clinician.

The 2024 communication also asked patients to tell their clinician about new or worsening depression, suicidal thoughts or unusual changes in mood or behavior, and it asked clinicians to monitor for those changes ^[2]. The 2026 communication advised clinicians to be prepared to explain that FDA found no increased risk after a comprehensive review, and to refer patients who disclose suicidal thoughts or behavior to mental health professionals for evaluation ^[1].

Both communications point people in distress to 988, the 988 Suicide and Crisis Lifeline. Calling or texting 988 connects a person with a counselor, and the Lifeline describes its service as free, confidential and available 24/7/365 ^[1][2][13].

How strong is this evidence, and what are its limits?

The evidence is reassuring but not complete, and the studies themselves say why. Each limitation below comes from the authors or the regulators.

• Suicide is rare. The Nordic authors said they could not assess small risk increases, and subgroup estimates, including a Swedish hazard ratio of 1.44 (95% CI 0.87 to 2.37), were imprecise ^[11].
• Most people in the Nordic study had type 2 diabetes, so results may not apply to people with obesity alone ^[11].
• Residual confounding is possible in every observational study. The tirzepatide study excluded people with prior suicidal ideation or attempts, so the highest-risk group was not studied, and its authors called the findings tentative and hypothesis-generating ^[12].
• Follow-up was short for several analyses: 6 months in the semaglutide cohort, 1 year in the tirzepatide cohort, and a mean of about 2.5 years in the Nordic study ^[10][11][12].
• Reports to FAERS often had limited information, and FDA said the events can be influenced by other factors, so the reports did not show a clear link ^[2].

Taken together, regulators in the U.S. and Europe found no causal association. That is different from proving no one is ever affected, which the data cannot do. FDA itself said in 2024 that suicidal thoughts or actions were rare in both GLP-1 users and control groups ^[2]. Two gaps the authors name are that most Nordic participants had type 2 diabetes and that the tirzepatide study excluded people with prior suicidal ideation or attempts ^[11][12].

What this means in practice

• The U.S. labels for Wegovy, Zepbound and Saxenda no longer carry a suicidal behavior and ideation warning, per their own revision tables ^[3][4][5].
• FDA's stated basis is a 91-trial meta-analysis and a 2.2-million-person claims study that found no increased risk ^[1].
• FDA still tells patients to report new or worsening depression, suicidal thoughts or unusual changes in mood or behavior to a health care professional ^[1][2].
• FDA's 2024 advice also said not to stop a GLP-1 medicine without first talking to a health care professional, since stopping may worsen the condition being treated ^[2].
• Report a mood change to your clinician whatever you think the cause is; the clinician can sort out the possibilities.
• If you are in distress, call or text 988 (the 988 Suicide and Crisis Lifeline), which is free, confidential and available 24/7/365, or contact emergency services if you may be in immediate danger ^[1][13].

When to talk to a clinician

Tell a clinician about new or worsening depression, anxiety, irritability, unusual changes in mood or behavior, or any thoughts of harming yourself. Bring up past mental health history before starting any weight-management medicine, because the prescriber needs the full picture. If you are having thoughts of suicide, do not wait for an appointment. Call or text 988, or contact emergency services right away ^[1][13].

At Healthy Weight Loss 4 U, every program begins with a clinician evaluation, and that evaluation is where to raise questions about mood, mental health history and any medicine you take. A licensed clinician decides whether any treatment is appropriate for you and what monitoring is needed. This article is general information and makes no promises about outcomes.

Frequently asked questions

Sources

1. FDA Requests Removal of Suicidal Behavior and Ideation Warning from Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications (Drug Safety Communication, Jan 13, 2026). U.S. Food and Drug Administration, 2026. www.fda.gov/drugs/drug-safety-communications/fda-requests-removal-suicidal-behavior-and-ideation-warning-glucagon-peptide-1-receptor-agonist-glp
2. 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 (Jan 11, 2024). U.S. Food and Drug Administration, 2024. www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type
3. WEGOVY (semaglutide) prescribing information, revised 05/2026. U.S. Food and Drug Administration (Drugs@FDA), 2026. www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s031,218316s00lbl.pdf
4. ZEPBOUND (tirzepatide) prescribing information, revised 04/2026. U.S. Food and Drug Administration (Drugs@FDA), 2026. www.accessdata.fda.gov/drugsatfda_docs/label/2026/217806Orig1s050lbl.pdf
5. SAXENDA (liraglutide) prescribing information, revised 02/2026. U.S. Food and Drug Administration (Drugs@FDA), 2026. www.accessdata.fda.gov/drugsatfda_docs/label/2026/206321s025lbl.pdf
6. WEGOVY (semaglutide) prescribing information, revised 03/2024 (section 5.9, now removed). U.S. Food and Drug Administration (Drugs@FDA), 2024. www.accessdata.fda.gov/drugsatfda_docs/label/2024/215256s011lbl.pdf
7. ZEPBOUND (tirzepatide) prescribing information, revised 09/2025 (section 5.9, now removed). U.S. Food and Drug Administration (Drugs@FDA), 2025. www.accessdata.fda.gov/drugsatFDA_docs/label/2025/217806s031lbl.pdf
8. EMA statement on ongoing review of GLP-1 receptor agonists (July 11, 2023). European Medicines Agency, 2023. www.ema.europa.eu/en/news/ema-statement-ongoing-review-glp-1-receptor-agonists
9. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 8-11 April 2024. European Medicines Agency, 2024. www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-8-11-april-2024
10. Association of semaglutide with risk of suicidal ideation in a real-world cohort (Wang W, Volkow ND, Berger NA, et al.). Nature Medicine 30:168-176, 2024. www.nature.com/articles/s41591-023-02672-2
11. GLP-1 Receptor Agonist Use and Risk of Suicide Death (Ueda P, Söderling J, Wintzell V, et al.). JAMA Internal Medicine 184(11):1301-1312, 2024. pmc.ncbi.nlm.nih.gov/articles/PMC11372654/
12. Association of tirzepatide and the risk of suicide in a real-world cohort (Yu W-S, Huang J-Y, Lo S-C, et al.). Frontiers in Psychiatry 16:1626103, 2025. pmc.ncbi.nlm.nih.gov/articles/PMC12667738
13. 988 Suicide & Crisis Lifeline. 988 Suicide & Crisis Lifeline, 2026. 988lifeline.org/

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