While semaglutide and liraglutide showed higher-than-expected reports of suicidal ideation in the FDA's adverse event database, no causal link to suicidality was found after accounting for confounding factors.
No causal link foundDespite elevated reports of suicidal ideation with semaglutide and liraglutide, Bradford Hill causality analysis found no evidence these drugs cause suicidality
What the researchers found
Semaglutide and liraglutide showed disproportionate reporting of suicidal ideation and 'depression/suicidal' events in the FDA Adverse Event Reporting System, with reporting odds ratios whose lower 95% confidence interval exceeded 1.0 (indicating statistical significance).
Critically, no disproportionate reporting of more severe outcomes — suicidal behavior, suicide attempts, or completed suicide — was observed for any FDA-approved GLP-1 receptor agonist. When the data was evaluated using Bradford Hill criteria for causality and confounding factors were considered, the researchers found no causal link between GLP-1 RAs and suicidality.
Why it matters
With tens of millions of people taking semaglutide and liraglutide, even a small increase in suicide risk would be a major public health concern. This analysis of the largest pharmacovigilance database in the world provides reassurance: while suicidal thoughts are reported more frequently with these drugs, the more serious outcomes (attempts and completions) are not elevated, and no causal link was found. This is critical context for the ongoing FDA investigation and for prescribers weighing risks and benefits.
How the study worked
Pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) database. Reports from 2005 through October 2023 were analyzed for suicidal ideation, depression/suicidal events, suicidal behavior, suicide attempts, and completed suicide associated with all FDA-approved GLP-1 receptor agonists. Data was compared against other glucose-lowering agents using reporting odds ratios (ROR), with significance defined as the lower 95% CI exceeding 1.0. Bradford Hill criteria were applied to evaluate potential causality.
What this study cannot tell us
FAERS is a voluntary reporting system subject to reporting bias, underreporting, and the inability to establish causation. The disproportionate reporting for semaglutide and liraglutide could reflect media attention and the Weber effect (increased reporting for newer, high-profile drugs). The analysis cannot control for all confounders — obesity and diabetes independently increase depression and suicidality risk. Reporting odds ratios measure disproportionality in reporting, not actual risk. The study period predates the massive expansion of GLP-1 use for weight loss in otherwise healthy populations.
How to read the evidence
This is a pharmacovigilance (signal detection) study using the FDA's voluntary adverse event reporting database. While it covers a massive dataset, FAERS cannot establish causation, is subject to reporting bias, and lacks the control and rigor of randomized clinical trials. It's valuable for safety signal assessment but not definitive.
When this study was published
Published in early 2024, this study is highly timely and directly relevant to the ongoing FDA safety review of GLP-1 drugs and suicidality that was announced in early 2024.
The bigger picture
This study is part of the broader pharmacovigilance effort around GLP-1 drugs as their use has exploded for obesity and diabetes. The EMA's initial safety signal triggered worldwide concern, and the FDA launched its own investigation. This FAERS analysis — one of the first systematic evaluations — provides important context showing that the signal is likely driven by reporting bias and confounders (depression is more common in obese and diabetic populations) rather than a true drug effect. It sets the stage for more definitive analyses from clinical trial data and real-world evidence studies.
Questions still open
- Will the ongoing FDA investigation using clinical trial data and real-world evidence confirm or contradict these FAERS findings?
- Is the elevated reporting of suicidal ideation driven by the Weber effect and media attention rather than a true pharmacological signal?
- Should patients with pre-existing depression or suicidal history be screened more carefully before starting GLP-1 drugs?
Common questions
Should I be worried about suicidal thoughts on Ozempic or Wegovy?
What is FAERS and why can't it prove a drug causes side effects?
Read the original research
The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS).
Expert opinion on drug safety, 23(1), 47-55
Citation
McIntyre, Roger S; Mansur, Rodrigo B; Rosenblat, Joshua D; Kwan, Angela T H. (2024). The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS).. Expert opinion on drug safety, 23(1), 47-55. https://doi.org/10.1080/14740338.2023.2295397