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Do GLP-1 medicines affect mental health? What studies found on depression and suicidal thoughts

Reports of suicidal thoughts on semaglutide made headlines in 2023. Since then, regulators and researchers have looked at data from millions of people. Here is what they found, and what is still uncertain.

By 7 min read
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The short version
  • An FDA review of 91 placebo-controlled trials with 107,910 patients found no increased risk of suicidal thoughts, depression or anxiety with GLP-1 medicines, and in January 2026 the FDA asked for the suicide warning to be removed from weight-loss labels.1
  • Pooled trial data for semaglutide (Wegovy) and tirzepatide (Zepbound) showed depression scores slightly lower than placebo, and suicidal thoughts in about 1% or fewer of people in both groups.5,6
  • The trials mostly left out people with serious mental illness, so the evidence for that group is thinner.
  • If you have thoughts of harming yourself, contact your doctor, or call or text 988 in the US. Elsewhere, call your local emergency number.
If you are struggling right now: in the US, call or text 988 (Suicide and Crisis Lifeline), any time of day. Outside the US, call your local emergency number or go to the nearest emergency department. Tell your prescriber about any new or worsening low mood, anxiety or thoughts of self-harm.

Why people worried about GLP-1s and mental health

In 2023, reports of suicidal thoughts in people taking semaglutide (Ozempic, Wegovy) and liraglutide (Saxenda) led regulators in Europe and the US to open reviews. At the time, the Wegovy label carried a warning, section 5.9, "Suicidal Behavior and Ideation," which said to monitor for depression or suicidal thoughts.11 The Zepbound label for tirzepatide carried the same warning until 2026.4

Reports like these are a signal to investigate, not proof. Obesity itself is linked to higher rates of depression, so some reports are expected in any large group of people treated for it. The question is whether the medicine raises the risk.

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What did the FDA and EMA conclude?

In January 2024 the FDA said its preliminary review had found no evidence of a link, but that the small number of cases left uncertainty. It then ran a larger analysis.1

91 trialsplacebo-controlled, 107,910 patients (60,338 on a GLP-1, 47,572 on placebo): no increased risk
2,243,138new users with type 2 diabetes in FDA's Sentinel system: no increased risk of self-harm vs SGLT2 inhibitors

On January 13, 2026, the FDA concluded there was no increased risk of suicidal thoughts or behavior, and no increased risk of anxiety, depression, irritability or psychosis in the trial data. It asked the makers of Saxenda, Wegovy and Zepbound to remove the warning.1 The current Wegovy and Zepbound labels now list "Suicidal Behavior and Ideation" as removed in 02/2026 under Recent Major Changes.3,4

Europe reached the same view earlier. In April 2024, the EMA's safety committee (PRAC) said that "the available evidence does not support a causal association" between GLP-1 medicines and suicidal or self-injurious thoughts, and that no change to product information was needed.2

What did the clinical trials show?

Trials are the strongest evidence because people are randomly assigned to the drug or placebo. Two pooled analyses looked at mental health using standard questionnaires: the PHQ-9 for depression and the Columbia scale for suicidal thoughts.

AnalysisWhoDepressionSuicidal thoughts
Semaglutide 2.4 mg, STEP 1, 2, 3 (68 weeks)3,377 adults with overweight or obesity, no known major psychiatric illnessLess likely to move to a more severe PHQ-9 category (odds ratio 0.63)1% or fewer, no difference from placebo5
Tirzepatide, SURMOUNT-1, -2, -3 (72 weeks)4,056 adults with obesity, no known major psychiatric illness18.2% vs 24.3% moved to a more severe category0.6% on tirzepatide and 0.6% on placebo6
 Post hoc pooled analyses. Sources: Wadden et al., JAMA Intern Med 2024 and Obesity 2026.5,6

In the semaglutide analysis, the difference in depression scores was small (0.56 points on a 27-point scale) and the authors say it was not clinically meaningful.5 In the tirzepatide analysis, nonfatal suicidal behavior occurred in 0.1% of people on tirzepatide and none on placebo, and other psychiatric side effects were generally similar.6 Both analyses were funded or co-authored by the drug makers.

What did real-world studies find?

Observational studies follow much larger groups in everyday care. They can't prove cause, but they can catch rare events that trials miss.

  • Semaglutide in 240,618 people with overweight or obesity (US health records, 2024). Compared with other weight-loss medicines, semaglutide was linked to a lower risk of new suicidal thoughts (hazard ratio 0.27) and recurrent ones (0.44) over 6 months. Results were similar in 1,589,855 people with type 2 diabetes.7
  • Suicide deaths in Sweden and Denmark (2024). Among 124,517 people starting a GLP-1 medicine, mostly for type 2 diabetes, suicide death was rare: 0.23 vs 0.18 per 1,000 person-years compared with SGLT2 inhibitors (hazard ratio 1.25, 95% CI 0.83–1.88, not statistically significant). There was no increase in new depression or anxiety (hazard ratio 1.01).8
  • FDA Sentinel study (2026). Intentional self-harm was 1.13 per 1,000 person-years on GLP-1s vs 1.22 on SGLT2 inhibitors (hazard ratio 0.93), with similar results in people with a psychiatric history.9
  • People already treated for depression (2026). In 34,761 matched pairs with type 2 diabetes on antidepressants, starting a GLP-1 was not linked to more suicidality than starting an SGLT2 inhibitor (hazard ratio 0.88).10

What isn't known yet

  • People with serious mental illness. The trials excluded people with major psychiatric conditions. The SURMOUNT authors say more study in this group may be warranted.6
  • Weight-loss users specifically. Most large real-world studies are in people with type 2 diabetes, and newer drugs such as tirzepatide have less follow-up.
  • Individual reactions. Population studies can't rule out that a few people feel worse. Nausea, eating much less, fast body changes, or stopping a medicine can all affect mood.

Removing the label warning does not mean mood changes should be ignored. The FDA still advises patients to tell a health care professional about new or worsening depression, suicidal thoughts, or unusual changes in mood or behavior.1 Decisions about your treatment belong with your prescriber.

For other side effects, see GLP-1 nausea and stomach side effects, hair loss on GLP-1s and GLP-1s and alcohol.

Common questions

Does Ozempic or Wegovy cause depression?

Large studies have not found that. In a pooled analysis of 3,377 adults with overweight or obesity in the STEP 1, 2 and 3 trials, depression scores were slightly lower on semaglutide than placebo after 68 weeks, and an FDA meta-analysis of 91 placebo-controlled trials found no increased risk of depression. People with major psychiatric illness were mostly not included in the trials.

Does Zepbound have mental health side effects?

In a pooled analysis of 4,056 adults in the SURMOUNT-1, -2 and -3 trials, 0.6% on tirzepatide and 0.6% on placebo reported suicidal thoughts, and fewer people on tirzepatide moved to a more severe depression category (18.2% vs 24.3%). In early 2026 the FDA asked for the suicidal behavior warning to be removed from the Zepbound label.

Does tirzepatide cause anxiety?

The evidence so far does not show that. An FDA meta-analysis of 91 placebo-controlled GLP-1 trials with 107,910 patients found no increased risk of anxiety, depression, irritability or psychosis. If you notice new anxiety or mood changes, tell your prescriber.

Why did the FDA remove the suicidal thoughts warning from GLP-1 labels?

On January 13, 2026, the FDA said its review found no increased risk of suicidal thoughts or behavior with GLP-1 medicines. The review included 91 trials with 107,910 patients and a cohort of 2,243,138 people with type 2 diabetes. It asked for the warning to be removed from the Saxenda, Wegovy and Zepbound labels.

Sources

  1. U.S. Food and Drug Administration. FDA Requests Removal of Suicidal Behavior and Ideation Warning from Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications. Drug Safety Communication, January 13, 2026. fda.gov
  2. European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 8-11 April 2024. ema.europa.eu
  3. WEGOVY (semaglutide) injection and tablets. Prescribing information, Recent Major Changes. Novo Nordisk. Revised 06/2026. DailyMed
  4. ZEPBOUND (tirzepatide) injection. Prescribing information, Recent Major Changes. Eli Lilly and Company. Revised 08/2026. DailyMed
  5. Wadden TA, Brown GK, Egebjerg C, et al. Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials. JAMA Intern Med. 2024;184(11):1290-1300. PubMed · Full text (PMC)
  6. Wadden TA, Oquendo MA, Kushner RF, et al. Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT. Obesity (Silver Spring). 2026;34(3):565-578. PubMed · Full text (PMC)
  7. Wang W, Volkow ND, Berger NA, et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med. 2024;30(1):168-176. PubMed · Full text (PMC)
  8. Ueda P, Söderling J, Wintzell V, et al. GLP-1 Receptor Agonist Use and Risk of Suicide Death. JAMA Intern Med. 2024;184(11):1301-1312. PubMed · Full text (PMC)
  9. Kuzucan A, Tran V, Jones JT, et al. Association of GLP-1 receptor agonists with intentional self-harm in patients with type 2 diabetes: a Sentinel Distributed Database study. BMJ Open Diabetes Res Care. 2026;14(2):e005840. PubMed · Full text (PMC)
  10. Chang Y, Hsieh MH, Ju PC, et al. Risk of Psychiatric Worsening With GLP-1 Receptor Agonist Use in Patients With Type 2 Diabetes and Treated Depression. Diabetes Obes Metab. 2026;28(8):7048-7057. PubMed · Full text (PMC)
  11. WEGOVY (semaglutide) injection. Prescribing information, section 5.9, as listed in 04/2024 (before the 2026 removal). DailyMed
This article summarises published research for general information. It is not medical advice and does not replace advice from your own care team. Never change a medication or dose without talking to your prescriber.

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