Study 33 of 60Semaglutide literaturebiorxiv-preprint · Observational2026

Neuro-Adverse Events Associated with GLP-1 Receptor Agonists: A Study Based on the FAERS Database and External Validation Using NHANES Database

GLP-1 receptor agonists, including semaglutide, are associated with significant neuropsychiatric safety signals, warranting careful monitoring in clinical practice.

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this study against the rest of the semaglutide corpus

Preclinical

Observational · this one

Open-label

Randomised

Reviews

Summary and findings

This study evaluated neuro-adverse events associated with GLP-1 receptor agonists, including semaglutide, using FAERS and NHANES databases. The analysis identified significant neuro-adverse event signals, particularly highlighting muscle atrophy for semaglutide. The study also reported increased depression odds and reduced sleep hours among GLP-1RA users.

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ROR 3.94; 95%CI 3.42-4.54 for muscle atrophy with semaglutide.2026

Abstract

The authors’ words, as biorxiv-preprint supplied them

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely prescribed for type 2 diabetes and obesity, yet their neuropsychiatric safety profile remains incompletely characterized. We aimed to systematically evaluate neuro-adverse event (AE) signals for six GLP-1RAs and to validate key findings using population-based data. Methods We conducted disproportionality analysis of FAERS data for semaglutide, liraglutide, dulaglutide, tirzepatide, exenatide, and lixisenatide. RORs were calculated for 93 predefined neuro-AE MedDRA PTs across 11 neurological categories. External validation used NHANES 2013-2018 (n=17,057; 70 GLP-1RA users) with survey-weighted regression. Results We identified 41 significant neuro-AE signals. Semaglutide showed the strongest neuromuscular signal, muscle atrophy (ROR 3.94; 95%CI 3.42-4.54), corroborated by tirzepatide (ROR 2.35; 95%CI 2.04-2.71). Exenatide generated the highest psychiatric signal: nervousness (ROR 4.03; 95%CI 3.70-4.40). NHANES confirmed higher depression odds (OR 2.05; 95%CI 1.32-3.19; P=0.001) and reduced sleep hours (beta -0.35; P=0.033). Conclusions GLP-1RAs carry multiple neuropsychiatric safety signals, including muscle atrophy as a potential class effect and depression risk corroborated by population-level data. These findings support heightened clinical monitoring.

Elsewhere in the Semaglutide corpus

DGLP-1s and criminality: US trial will test whether semaglutide can fight crime.BMJ (Clinical research ed.) · 2026—DThe pharmacotherapy for pediatric obesity: insights and challenges from adult weight-loss medications.Journal of diabetes and metabolic disorders · 2026 · Not reported in abstract.review BCardiovascular outcomes with tirzepatide versus semaglutide in type 2 diabetes.Journal of diabetes and metabolic disorders · 2026 · n=271685 · 4.6% primary composite outcome incidence in tirzepatide group vs. 5.5% in semaglutide group, ARD -0.9%, 95% CI -1.01 to -0.77, HR 0.9, 95% CI 0.92─0.96.Human BWeight-Loss Outcomes After Sleeve Gastrectomy Versus Tirzepatide in a Minority Cohort With Severe Obesity: Results From a Propensity Score Matched Cohort.Clinical obesity · 2023 · 30% TWL and 12 kg/m² BMI reduction for SG at 12 months, p < 0.001.Human DSemaglutide and Suicidality in Adults with Overweight or Obesity: A Bayesian Meta-Analysis of Randomized Trialsbiorxiv-preprint · 2026 · Completed suicide: pooled OR 1.56 (95% CrI 0.55–4.67), P(OR > 1) = 80.6%, n=17,086 semaglutide vs 15,304 placebo.review BWeight loss with a lower dose compounded semaglutide and behavioral weight management program: A real-world matched retrospective cohort studybiorxiv-preprint · 2026 · At 16 weeks, NMGP users lost 8.3% of their baseline weight.Human