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, Год журнала: 2024, Номер 82, С. 82 - 91

Опубликована: Март 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.

Язык: Английский

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

JAMA Internal Medicine, Год журнала: 2024, Номер unknown

Опубликована: Сен. 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 )

Язык: 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, Год журнала: 2024, Номер 67(11), С. 2471 - 2480

Опубликована: Авг. 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

Язык: Английский

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Association between glucagon‐like peptide‐1 receptor agonists and risk of suicidality: A comprehensive analysis of the global pharmacovigilance database

Diabetes Obesity and Metabolism, Год журнала: 2024, Номер 26(11), С. 5183 - 5191

Опубликована: Авг. 19, 2024

To evaluate the potential association between suicidality and glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well other medications used for obesity diabetes, using comprehensive global data.

Язык: Английский

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Neuropsychiatric adverse events associated with Glucagon-like peptide-1 receptor agonists: a pharmacovigilance analysis of the FDA Adverse Event Reporting System database

European Psychiatry, Год журнала: 2025, Номер 68(1)

Опубликована: Янв. 1, 2025

Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used due to their profound efficacy in glycemic control and weight management. Real-world observations have revealed potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs. This study aimed comprehensively investigate characterize these AEs Methods We analyzed GLP-1RA reaction reports using the FDA Adverse Event Reporting System database. Disproportionality analysis reporting odds ratio (ROR) identified eight categories of conducted descriptive time-to-onset (TTO) analyses explored AE signals among individual GLP-1RAs for loss diabetes mellitus (DM) indications. Results 25,110 cases GLP-1RA-related AEs. showed an association headache (ROR 1.74, 95% confidence interval [CI] 1.65–1.84), migraine 1.28, 95%CI 1.06–1.55), olfactory sensory nerve abnormalities 2.44, 1.83–3.25; ROR 1.69, 1.54–1.85). Semaglutide a moderate suicide-related signal population 2.55, 1.97–3.31). The median TTO was 16 days (interquartile range: 3–66 days). Conclusions In this study, we and, first time, detected positive migraine, abnormalities, abnormalities. also observed semaglutide, population. provides reliable basis further investigation However, as exploratory our findings require confirmation through large-scale prospective studies.

Язык: Английский

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An analysis on the role of glucagon-like peptide-1 receptor agonists in cognitive and mental health disorders

Nature Mental Health, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Abstract Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel drugs approved for diabetes and obesity. They acknowledged as a major scientific breakthrough. In addition to their metabolic effects, these medications act on other bodily systems involved in the physiopathology of various neurological psychiatric disorders. Several stakeholders calling more research investigate repurposing potential GLP-1RAs cognitive mental disorders, while others advocate better assessment safety profile from neuropsychiatric perspective. this Analysis, we searched relevant literature effects across range illnesses, gathering describing available pre-clinical mechanistic (278 studies) clinical (96 evidence substance-use psychotic mood anxiety eating others. By leveraging translational insights data, consider implications practice propose avenues further research.

Язык: Английский

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Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study

BMJ, Год журнала: 2025, Номер unknown, С. e080679 - e080679

Опубликована: Фев. 26, 2025

Abstract Objective To determine whether the use of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with an increased risk suicidal ideation, self-harm, and suicide among patients type 2 diabetes compared dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Design Active comparator, new user cohort study. Setting Primary care practices contributing data to UK Clinical Practice Research Datalink linked Hospital Episodes Statistics Admitted Patient Care Office for National Death Registration databases. Participants Patients diabetes. Exposures Two cohorts were assembled, first composed who started continued on GLP-1 DPP-4 between 1 January 2007 31 December 2020 second SGLT-2 2013 2020. Both followed until 29 March 2021. Main outcome measures The primary was suicidality, defined as a composite suicide. Secondary outcomes each these events considered separately. Propensity score fine stratification weighted Cox proportional hazards models fitted estimate hazard ratios 95% confidence intervals (CIs) average treatment effect treated patients. Results included 36 082 agonist users (median follow-up 1.3 years) 234 028 inhibitor 1.7 years). In crude analyses, incidence suicidality (crude rates 3.9 v 1.8 per 1000 person years, respectively; ratio 2.08, CI 1.83 2.36). This decreased null value after confounding factors accounted (hazard 1.02, 0.85 1.23). 32 336 1.2 96 212 Similarly, in analyses 4.3 2.7 years; 1.60, 1.37 1.87) but not (0.91, 0.73 1.12). Similar findings observed when analysed separately both cohorts. Conclusions this large study,

Язык: Английский

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GLP-1 agonists and risk of suicidal thoughts and behaviours: Confound by indication once again? A narrative review

European Neuropsychopharmacology, Год журнала: 2024, Номер 87, С. 29 - 34

Опубликована: Июль 27, 2024

Glucagon-like peptide-1 (GLP-1) agonists have been successfully used in clinical practice for the treatment of diabetes and obesity, offering significant benefits. However, concerns regarding their potential link to psychiatric side effects, like suicidal thoughts behaviours (STB) emerged. This narrative review investigates complex interplay between GLP-1 STB, focusing on biological stress induced by rapid weight loss, psychological social consequences, similar mechanism with addiction, evaluative lens Bradford Hill criteria causality. While can contribute substantial health improvements, they also introduce stressors. Disruptions homeostasis from quick reduction elevate cortisol norepinephrine levels, heightening risk for, or exacerbation STB. Psychological factors, including unfulfilled expectations identity changes after compound these risks. Utilizing reveals insufficient evidence a direct causal Yet, indirect effects related metabolic disturbances associated loss call cautious approach. Used carefully targeted populations may even emerge as protective agents against Therefore, it is crucial monitor patients during screen preexisting mental conditions. If detected, appropriate management should be applied. Future studies aim at optimizing dosing schedules mitigate adverse further investigate possible STB prevention.

Язык: Английский

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Risk of Suicide, Hair Loss, and Aspiration with GLP1-Receptor Agonists and Other Diabetic Agents: A Real-World Pharmacovigilance Study

Cardiovascular Drugs and Therapy, Год журнала: 2024, Номер unknown

Опубликована: Сен. 12, 2024

Язык: Английский

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GLP-1 and its analogues: Does sex matter?

Endocrinology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 22, 2024

Abstract While obesity and diabetes are prevalent in both men women, some aspects of these diseases differ by sex. New blockbuster class therapeutics, Glucagon-like peptide 1 (GLP-1) analogues (e.g. semaglutide), shows promise at curbing diseases. This review will address the topic sex differences endogenous therapeutic actions GLP-1 its analogues. Work on human studies animal research be reviewed. Preclinical data mechanisms potential system as well effect analogues, focusing effects drugs brain behavior relating to appetite metabolism, highlighted. Moreover, recent clinical evidence obesity, diabetes, cardiovascular disease discussed. Lastly, we for role mood reproductive function, with particular attention differences. Overall, while did not find many qualitative clinically approved a growing body literature highlights quantitative response an interaction therapeutics estrogens. What also clearly emerges is paucity female models or women very basic science GLP-1, gaps that should urgently mended, given popularity medications especially women.

Язык: Английский

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