Global Study Builds on Previous Research Linking Semaglutide & Suicide: Daily Dose

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On August 26, 2024, we reported on a study published in JAMA Network Open that examined potential signals for suicidal and self-injurious adverse drug reactions (ARDs) associated with the glucagon-like peptide-1 receptor agonists (GLP-1RAs) semaglutide and liraglutide.

The study

Researched conducted the disproportionality analysis using the WHO global database of suspected ARDs. They calculated the reporting odds ratio (ROR) and the Bayesian information component (IC) with 95% confidence intervals (CIs) to measure the disproportionality of reporting suicidal and self-injurious ADRs associated with the GLP-1 RAs compared to other medications. A disproportionality signal was considered significant when the lower limits of the ROR and IC were above 1 and 0, respectively.

To explore potential confounders, investigators performed sensitivity analyses to examine cases with coreported use of antidepressants and benzodiazepines and to compare semaglutide and liraglutide with other drugs prescribed for similar indications, such as dapagliflozin, metformin, and orlistat.

The findings

Among more than 36 million total reports in the WHO database, investigators identified 107 (mean age, 48 years; 55% women) and 162 (median age, 47 years; 61% women) cases of suicidal and/or self-injurious ARDs that were reported between November 2000 and August 2023 with semaglutide and liraglutide, respectively.

A significant disproportionality was only observed for semaglutide-associated suicidal ideation (ROR 1.45, 95% CI 1.18-1.77; IC 0.53, 95% CI 0.19-0.78) compared with all medications. This association remained significant in patients with coreported use of antidepressants (ROR 4.45, 95% CI 2.52-7.86; IC 1.96, 95% CI 0.98-2.63) and benzodiazepines (ROR 4.07, 95% CI 1.69-9.82; IC 1.67, 95% CI 0.11-2.65) when compared with dapagliflozin (ROR 5.56, 95% CI 3.23-9.60; IC 0.70, 95% CI 0.36-0.95), metformin (ROR 3.86, 95% CI 2.91-5.12; IC 1.20, 95% CI 0.94-1.53), and orlistat (ROR 4.24, 95% CI 2.69-6.69; IC 0.70, 95% CI 0.36-0.95).

Authors' comment

"A detected signal of semaglutide-associated suicidal ideation warrants urgent clarification."

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