Summary of Evidence and Clinical Judgments.
Summary of Evidence and Clinical Judgments.
| Question | Evidence base | Certainty (GRADE) | Judgment |
|---|---|---|---|
| Do GLP-1 RAs increase suicide / self-harm in adults with diabetes or obesity? | RCT meta-analyses; active-comparator cohorts; regulatory reviews | Moderate | No consistent increase demonstrated |
| Do GLP-1 RAs increase incident depression or anxiety? | RCT meta-analyses; active-comparator cohorts | Low | No class-wide increase; comparator-sensitive variation remains |
| Does available tirzepatide-specific evidence show excess psychiatric harm? | Post hoc pooled RCT analysis; one real-world cohort | Low | No signal of increased risk in available evidence |
| Are pharmacovigilance signals sufficient to infer causality? | EudraVigilance; FAERS; WHO VigiBase | Very low | No—signal detection only |
| Should current practice change because of suicidality concerns alone? | Totality of evidence; EMA / FDA reviews | Moderate | No class-wide contraindication; clinically monitor higher-risk patients |
EMA, European Medicines Agency; EudraVigilance, European Union adverse event reporting database; FAERS, FDA Adverse Event Reporting System; FDA, US Food and Drug Administration; GLP-1 RAs, glucagon-like peptide-1 receptor agonists; GRADE, Grading of Recommendations Assessment, Development and Evaluation; RCT, randomized controlled trial; VigiBase, World Health Organization global pharmacovigilance database; WHO, World Health Organization.