---
type: source
title: "Psychiatric and Psychological Adverse Effects Associated with Dulaglutide, Semaglutide, and Liraglutide: A VigiBase Study"
author: "ScienceDirect / Clinical Nutrition (multiple authors)"
url: https://pubmed.ncbi.nlm.nih.gov/40617160/
date: 2025-01-01
domain: health
secondary_domains: []
format: paper
status: unprocessed
priority: high
tags: [glp1, pharmacovigilance, eating-disorders, vigibase, psychiatric-adverse-events, semaglutide, class-effect]
intake_tier: research-task
---

## Content

Primary pharmacovigilance study using VigiBase® (multinational WHO adverse drug reaction database) analyzing 2,061,901 reports through December 1, 2024 for three GLP-1 receptor agonists: dulaglutide, semaglutide, and liraglutide.

Key findings:
- EATING DISORDERS: significant signal across ALL THREE GLP-1 RAs; aRORs between 4.17 and 6.80 — highest magnitude psychiatric signal in the study
- Semaglutide additional signals: depressed mood disorders (aROR 1.70, 95%CI 1.57-1.84); suicidality (aROR 1.45, 95%CI 1.29-1.63); anxiety (aROR 1.26, 95%CI 1.18-1.35)
- Sensitivity analysis: no signals before June 4, 2021 (Wegovy obesity approval date) — suggests the eating disorder signal emerged SPECIFICALLY in the obesity treatment population, not in the prior metabolic population
- The pre-Wegovy absence of signal aligns with RCT data from metabolic trials (no eating disorder signal in T2D populations)
- The post-Wegovy emergence implies the risk is specific to: (a) patients seeking GLP-1 for weight management specifically, and/or (b) the higher weight-loss doses used in obesity treatment vs. metabolic indications

Key limitation explicitly stated: the database did not contain information on pre-existing psychiatric conditions in patients reporting AEs — researchers could not distinguish medicine-induced reactions from events related to patients' ongoing health conditions (i.e., cannot rule out indication bias).

## Agent Notes
**Why this matters:** This is the PRIMARY quantitative evidence for the eating disorder signal. The class-effect finding (all three agents, not just semaglutide) is the most important detail — it suggests the signal is pharmacological, not drug-specific, which strengthens the mechanism hypothesis. The Wegovy cutoff finding is equally important: the signal is specific to the obesity treatment population, not metabolic patients, which either means (a) the higher doses create more risk, or (b) people with obesity/weight preoccupation are more ED-vulnerable, or (c) the obesity treatment population includes more people with undetected ED histories.

**What surprised me:** That no signals appeared before June 4, 2021 — this is strong evidence that the signal is NOT explained by years of metabolic use (T2D, which began much earlier). The risk is specific to the obesity-treatment population and/or the higher weight-management doses. This is the most important piece of evidence for differentiating between indication bias and drug effect.

**What I expected but didn't find:** Specific breakdown of the eating disorder signal by subtype (BED vs. AN vs. atypical AN). The aggregated eating disorder category prevents distinguishing whether GLP-1 is triggering restrictive EDs (theoretically harmful via appetite suppression) or BED (for which it may be therapeutic). The signal might be predominantly reported as BED events in people discovering they have improved — or predominantly restrictive events in people worsening.

**KB connections:**
- [[human-in-the-loop clinical AI degrades to worse-than-AI-alone because physicians both de-skill from reliance and introduce errors]] — parallel: the automation of appetite suppression through pharmacology disrupts the biological feedback loop that maintains normal eating behavior
- [[AI scribes reached 92 percent provider adoption]] — GLP-1 prescription similarly reached mass adoption before safety signal was fully characterized

**Extraction hints:** CRITICAL claim: "GLP-1 eating disorder pharmacovigilance signal (aROR 4.17-6.80) is a class effect that emerged specifically in the obesity treatment population after June 2021, not in the prior metabolic population, suggesting the risk is either dose-dependent or population-selection-dependent." This claim is specific, challengeable, and has clinical implications for prescribing criteria.

**Context:** VigiBase is the WHO's multinational pharmacovigilance database — larger and more global than FAERS. aROR (adjusted Reporting Odds Ratio) controls for multiple adverse events in same reports. This is the most robust pharmacovigilance evidence available for this signal.

## Curator Notes (structured handoff for extractor)
PRIMARY CONNECTION: [[GLP-1 receptor agonists are the largest therapeutic category launch in pharmaceutical history but their chronic use model makes the net cost impact inflationary through 2035]]
WHY ARCHIVED: The primary quantitative source for the eating disorder pharmacovigilance signal — all downstream claims about aROR values should cite this paper
EXTRACTION HINT: The June 2021 temporal boundary is the key evidentiary detail. Extractor should center the claim on this finding — it's what distinguishes this signal from general GLP-1 psychiatric risk.
