Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 14, 2024

Abstract Background Establishing whether there is a potential relationship between glucagon-like peptide 1 receptor agonists (GLP-1RAs) and suicidal or self-injurious behaviors (SSIBs) crucial for public safety. This study investigated the association GLP-1RAs SSIBs by exploring FDA Adverse Event Reporting System (FAERS) database. Methods A disproportionality analysis was conducted using post-marketing data from FAERS repository (2018 Q1 to 2022 Q4). SSIB cases associated with were identified analyzed through information component. The parametric distribution goodness-of-fit test employed analyze time-to-onset, Ω shrinkage used evaluate effect of co-medication on occurrence SSIBs. Results In total, 204 GLP-1RAs, including semaglutide, liraglutide, dulaglutide, exenatide, albiglutide, in Time-of-onset revealed no consistent mechanism latency patients receiving GLP-1RAs. did not indicate an Co-medication 81 antidepressants, antipsychotics, benzodiazepines, which may be proxies mental health comorbidities. Conclusions We found signal disproportionate reporting GLP-1RA use Clinicians need maintain heightened vigilance premedicated neuropsychotropic drugs. contributes greater acceptance type 2 diabetes mellitus obesity. Graphical

Language: Английский

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Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(8), P. e2423385 - e2423385

Published: Aug. 20, 2024

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained use primarily due to their weight-reduction effects, although a regulatory review was undertaken for potential suicidality concern.

Language: Английский

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GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 75, P. 102782 - 102782

Published: Aug. 30, 2024

Language: Английский

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Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis

European Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 82, P. 82 - 91

Published: March 19, 2024

The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA). aim this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin orlistat as comparators. Descriptive pharmacovigilance disproportionality analyses performed. A total 209,354 ADRs were reported, including 59,300 serious cases. Of those, a 5378 disorder cases, 383 'serious' cases related selected registered during 2005–2023. After unmasking, 271 where individual GLP-1 RA implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) 1.64), exenatide 67; ROR 0.80), semaglutide 61; 2.03), dulaglutide 45; 0.84), tirzepatide 5; 1.76) albiglutide 2; 0.04). greater association between these with observed, but not orlistat. With regards preferred terms (PTs), 42 deaths 13 completed suicides recorded. Suicidal ideation recorded in n 236 for 6/7 (excluding lixisenatide). Suicide/self-injury pertaining semaglutide; tirzepatide; characterised, although lower than metformin. It is postulated that rapid weight loss achieved can trigger significant emotional, biological, psychological responses, hence possibly impacting on suicidal self-injurious ideations. current approach, no causality link use any be inferred. There need further research vigilance prescribing, particularly patients co-existing disorders.

Language: Английский

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Glucagon-like Peptide-1 Receptor Agonists and Suicidal Ideation: Analysis of Real-Word Data Collected in the European Pharmacovigilance Database

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 147 - 147

Published: Jan. 23, 2024

Background: A potential risk of suicide associated with liraglutide or semaglutide treatments has recently emerged. Therefore, we decided to investigate the reporting probability suicidal events among glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Methods: retrospective pharmacovigilance study European Pharmacovigilance database was conducted for period from 1 January 2018 10 July 2023. Disproportionality analyses (reporting odds ratio, ROR) were performed assess GLP-1 RAs. Results: total 230 reports identified. The most reported RA (38.3%), followed by (36.5%) and dulaglutide (16.1%). ideation (65.3%) attempt (19.5%). analysis found a higher than (ROR, 2.05; 95%CI, 1.40–3.01) exenatide 1.81; 1.08–3.05). In same way, 3.98; 2.73–5.82) 3.52; 2.10–5.92). On contrary, lower 0.51; 0.38–0.69). Conclusions: Suicidal mostly liraglutide, which also significantly probabilities compared other GLP1 Although this provides frequencies suicide-related RAs, establishing causality requires further investigation, will probably be addressed Risk Assessment Committee Medicine Agency in future.

Language: Английский

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Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology

JAMA Internal Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Importance Obesity is associated with numerous psychosocial complications, making psychiatric safety a consideration for treating people obesity. Few studies have investigated the of newly available antiobesity medications. Objective To evaluate subcutaneous semaglutide, 2.4 mg, once weekly in without known major psychopathology. Design, Setting, and Participants This post hoc analysis pooled data from randomized, double-blind, placebo-controlled, multicenter phase 3a STEP 1, 2, 3 trials (68 weeks; 2018-2020) 3b 5 trial (104 2018-2021) included adults overweight or obesity; 2 participants also had type diabetes. Trial designs been published previously. Interventions Semaglutide, vs placebo. Main Outcomes Measures Depressive symptoms suicidal ideation/behavior were assessed using Patient Health Questionnaire (PHQ-9) Columbia–Suicide Severity Rating Scale, respectively. Psychiatric nervous system disorder adverse events investigated. Results 3377 (2360 women [69.6%]; mean [SD] age, 49 [13] years) 304 (236 [77.6%]; 47 [11] years). In trials, (SD) baseline PHQ-9 scores placebo groups 2.0 (2.3) 1.8 (2.3), respectively, indicating no/minimal depression. at week 68 (2.9) (3.3), respectively; estimated treatment difference (95% CI) between was −0.56 (−0.81 to −0.32) ( P < .001). treated semaglutide less likely shift (from 68) more severe category depression (odds ratio, 0.63; 95% CI, 0.50-0.79; Based on 1% fewer reported during treatment, no differences generally balanced groups. Similar results observed 5. Conclusions Relevance The this suggest that did not increase risk developing small but statistically significant reduction depressive (not considered clinically meaningful). People obesity should be monitored mental health concerns so they can receive appropriate support care. Registration ClinicalTrials.gov Identifiers: 1 NCT03548935 ), NCT03552757 NCT03611582 NCT03693430 )

Language: Английский

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Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: what do we know and future vistas

Expert Opinion on Drug Safety, Journal Year: 2024, Volume and Issue: 23(5), P. 539 - 542

Published: March 23, 2024

KEYWORDS: Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs)liraglutidesemaglutidetirzepatideweight lossobesityoverweightdiabetesdepressionsuicide

Language: Английский

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Glucagon-like Receptor-1 agonists for obesity: Weight loss outcomes, tolerability, side effects, and risks

Obesity Pillars, Journal Year: 2024, Volume and Issue: 12, P. 100127 - 100127

Published: Aug. 31, 2024

This review investigates the side effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide, semaglutide, and tirzepatide, medications known for their efficacy in promoting weight loss among individuals with obesity. The rationale is rooted understanding balance between therapeutic benefits associated risks.

Language: Английский

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Glucagon-Like Peptide-1 Receptor Agonists and Risk for Suicidal Ideation and Behaviors in U.S. Older Adults With Type 2 Diabetes

Annals of Internal Medicine, Journal Year: 2024, Volume and Issue: 177(8), P. 1004 - 1015

Published: July 15, 2024

A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation behaviors based on International Classification of Diseases codes.

Language: Английский

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Association of glucagon-like peptide-1 receptor agonists with suicidal ideation and self-injury in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study

Diabetologia, Journal Year: 2024, Volume and Issue: 67(11), P. 2471 - 2480

Published: Aug. 5, 2024

Abstract Aims/hypothesis Regulators worldwide are reviewing safety data on glucagon-like peptide-1 receptor agonists (GLP-1RA), following reports by the Icelandic Medicines Agency in July 2023 of suicidal ideation and self-injury (SIS) individuals taking liraglutide semaglutide. We aimed to assess risk SIS new users GLP-1RA when compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i) users, prescribed treat type diabetes obesity. Methods This is a cohort study combining several population-wide databases covering Spanish population five million inhabitants, including all adults obesity who initiated treatment either or SGLT-2i for from 2015 2021. To estimate comparative effect SIS, we employed user, active comparator design carried out multivariable Cox regression modelling inverse probability weighting (IPTW) based propensity scores. performed stratified sensitivity analyses. Results included 3040 patients initiating 11,627 SGLT-2i. When treated SGLT-2i, those group were younger (55 vs 60 years old, p <0.001), had more anxiety (49.4% 41.5%, sleep disorders (43.2% 34.1%, <0.001) depression (24.4% 19.0%, obese (35.1% BMI ≥40 15.1%, <0.001). After score weighting, standardised mean differences between groups <0.1 covariates, showing adequate balance at baseline after adjustment. In main per-protocol analyses found no evidence that increased incidence (HR 1.04; 95% CI 0.35, 3.14). Intention-to-treat resulted an HR 1.36 (95% 0.51, 3.61). excluding information using imputation missing values, respective HRs 0.89 0.26, 3.14) 1.29 0.42, 3.92). Stratified showed subgroups. Conclusions/interpretation Our findings do not support obesity; however, rarity events wide uncertainty size (although null, may be compatible as high threefold) calls cautious interpretation our results. Further studies, final evaluations regulatory bodies, called discard causal link suicidality. Graphical

Language: Английский

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