Semaglutide and Panic Attacks: Active-Comparator Disproportionality Analysis, Temporal Assessment of Notoriety Bias and Evidence Triangulation in Post-Marketing Pharmacovigilance
- Design
- Pharmacovigilance · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Population unclearUNKNOWN: the units are spontaneous FAERS reports and no age, sex, BMI or diabetes distribution is given for the reported cases; type 2 diabetes and obesity/weight management appear only as indication categories adjusted for, and a covariate is not the population (IN-062).
- Could weight loss explain it?
- Possiblypossibly, by the no-data default: no weight change, HbA1c or mediation analysis is reported, and adjustment for age, sex and indication addresses confounding, not mediation. The authors' own explanation for the signal's rise is notoriety bias after the July 2023 regulatory communication.
- Study tier
- Study tier 4VERY_LOW: a pharmacovigilance disproportionality analysis of spontaneous reports, which section 3 rates VERY_LOW. The active-comparator design and reported confidence intervals strengthen it against a crude signal, but reporting odds ratios cannot estimate incidence or establish causality, as the authors state, and the size of the signal moves with the reporting period.
- Assessment
- Version 2 · Two reviewers differed; settled by a recorded ruling · Nov 6, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
This analysis counted panic-attack reports in the FDA's adverse event reporting system from 2018Q1 to 2024Q4, comparing semaglutide with two drugs used for the same conditions. Panic attacks were recorded in 87 (0.26%) of 33 267 semaglutide reports, 28 (0.05%) of 54 282 dulaglutide reports and 13 (0.05%) of 25 380 empagliflozin reports. Crude reporting odds ratios of 5.08 and 5.12 fell after adjustment to 2.82 (95% CI 1.74-4.56) and 2.75 (95% CI 1.41-5.36), and to 1.38 (95% CI 0.69-2.75) and 1.14 (95% CI 0.48-2.68), no longer significant, among reports received before July 1, 2023; reports per 10 000 semaglutide reports then rose from 6.7 in 2018-2022 to 42.0 in 2023-2024. Across 12 studies, randomized trials and active-comparator observational cohorts did not show a consistent increase. Report counts cannot measure how often an event happens or show cause.
01Findings
What the study reported
- Drugs
- Semaglutide
- Comparator
- dulaglutide and empagliflozin as active comparators, with all other primary-suspect drugs in FAERS as a sensitivity reference set
- Primary outcome
- panic attack, identified by the MedDRA preferred term
- Effect
- Crude reporting odds ratios 5.08 versus dulaglutide and 5.12 versus empagliflozin, attenuating after adjustment to 2.82 and 2.75. Restricted to reports before July 1, 2023, crude RORs were 2.24 and 2.15, attenuating to 1.38 and 1.14 after adjustment. Against all other primary-suspect drugs the aROR was 1.48 overall and 0.76 before July 1, 2023. Reports per 10 000 semaglutide reports rose from 6.7 in 2018-2022 to 42.0 in 2023-2024 (drug-by-period interaction p = 0.007). Across 12 studies, trials and active-comparator cohorts showed no consistent increase.
- 95% confidence interval
- 95% CI 1.74-4.56 for the adjusted ROR versus dulaglutide and 95% CI 1.41-5.36 versus empagliflozin; 95% CI 0.69-2.75 and 95% CI 0.48-2.68 for the same comparisons before July 1, 2023
- P value
- drug-by-period interaction p = 0.007
- Follow-up
- Not stated
- Adverse events
- Panic attacks were recorded in 87 (0.26%) semaglutide reports, 28 (0.05%) dulaglutide reports and 13 (0.05%) empagliflozin reports; adjusted reporting odds ratios were 2.82 and 2.75 over the whole period but 1.38 and 1.14 before July 1, 2023.
- Limitations
- A disproportionality analysis of spontaneous reports, which the authors say is hypothesis-generating and cannot estimate incidence or establish causality; reporting rose sharply after the July 2023 regulatory communication, a pattern consistent with notoriety bias, and residual confounding by indication remains despite adjustment.
Who was studied
- Obesity status
- not reported in abstract
- Diabetes status
- not reported in abstract
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- not reported in abstract
- Inclusion exclusion
- individual case safety reports in FAERS from 2018Q1 to 2024Q4 in which semaglutide, dulaglutide or empagliflozin was the primary suspect drug
Study quality details
- Study design
- Pharmacovigilance analysis
- Sample size
- not extracted
- Randomization
- no
- Blinding
- n/a
- Comparator
- dulaglutide and empagliflozin as active comparators, with all other primary-suspect drugs in FAERS as a sensitivity reference set
- Follow up duration
- not stated
- Outcome type
- hard
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- UNKNOWN
- Statistical precision
- 95% confidence intervals reported throughout; panic attacks in 87, 28 and 13 reports for semaglutide, dulaglutide and empagliflozin
- Risk of bias
- not assessed
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- Authors declare no conflicts of interest.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[PURPOSE] To evaluate how confounding by indication and notoriety bias shape the apparent semaglutide-panic attack signal in the FDA Adverse Event Reporting System (FAERS) and to interpret this signal using an evidence-triangulation framework integrating randomized and observational studies. [METHODS] We conducted an active-comparator restricted disproportionality analysis of FAERS (2018Q1-2024Q4), including individual case safety reports in which semaglutide, dulaglutide or empagliflozin was the primary suspect drug. Panic attack was identified using the MedDRA preferred term. Crude and adjusted reporting odds ratios (RORs, aRORs) with 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age, sex and indication (Type 2 diabetes, obesity/weight management). Notoriety bias was assessed using prespecified temporal analyses (analyses restricted to reports received before July 1, 2023 and a drug-by-period comparison of 2018-2022 with 2023-2024) and reporting proportions per 10 000 reports. A sensitivity analysis used all other primary-suspect drugs in FAERS as the reference set. In parallel, we conducted a systematic review (MEDLINE, Embase, CENTRAL to November 24, 2025) of randomized trials, cohort and cross-sectional studies, pharmacovigilance analyses and case reports reporting panic attacks or acute anxiety outcomes with semaglutide. [RESULTS] Among 33 267 semaglutide, 54 282 dulaglutide and 25 380 empagliflozin reports, panic attacks were recorded in 87 (0.26%), 28 (0.05%) and 13 (0.05%) cases, respectively. Crude RORs were 5.08 (95% CI 3.32-7.78) versus dulaglutide and 5.12 (95% CI 2.86-9.17) versus empagliflozin, attenuating after adjustment to 2.82 (95% CI 1.74-4.56) and 2.75 (95% CI 1.41-5.36). In the pre-warning period crude RORs were 2.24 (95% CI 1.23-4.07) and 2.15 (95% CI 1.00-4.58), attenuating to 1.38 (95% CI 0.69-2.75) and 1.14 (95% CI 0.48-2.68) after adjustment. Panic-attack reports per 10 000 semaglutide reports rose from 6.7 in 2018-2022 to 42.0 in 2023-2024 (drug-by-period interaction p = 0.007). Against all other primary-suspect drugs, the aROR was 1.48 (95% CI 1.18-1.87) overall and 0.76 (95% CI 0.48-1.18) before July 1, 2023. Across 12 studies, randomized trials and active-comparator observational cohorts did not show a consistent increase in panic attacks or anxiety-related outcomes. [CONCLUSIONS] Crude FAERS analyses suggested a semaglutide-panic attack signal that attenuated after adjustment was no longer significant before the July 2023 regulatory communication and rose sharply thereafter in a pattern consistent with notoriety bias. Triangulation with randomized trials and active-comparator observational studies does not support a consistent pharmacological association. Disproportionality analyses are hypothesis-generating and cannot estimate incidence or establish causality. This case study illustrates how active-comparator design, temporal assessment of notoriety bias and evidence triangulation can improve the interpretation of post-marketing safety signals.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Nov 1, 2026 | 42946127 first ingestion |
| owner-review | Nov 6, 2026 | reviewed_by set to Carrie Schluter (2026-11-05) on the owner's own confirmation. The assessment is unchanged and still the auto-classifier's, so its extracted values stay withheld under the 2026-10-18 decision. |
| pubmed | Nov 8, 2026 | 42946127 duplicate matched on doi |