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

Summary

Using two active-comparator new-user cohorts from linked UK primary care and hospital/death records, GLP-1 receptor agonist use was not associated with higher risk of suicidality (suicidal ideation, self-harm, or suicide) versus DPP-4 inhibitors or SGLT-2 inhibitors. Median follow-up was 1.3–1.7 years in the first cohort with >270,000 participants.

Key Findings

• Two active-comparator new-user cohorts compared GLP-1 RAs to DPP-4 inhibitors and SGLT-2 inhibitors using propensity score fine stratification weighted Cox models.
• In the DPP-4 comparator cohort, 36,082 GLP-1 RA users and 234,028 DPP-4 users were included (median follow-up 1.3 vs 1.7 years).
• GLP-1 RA use was not associated with increased risk of suicidality versus either comparator class.

Clinical Implications

Clinicians can reassure patients that GLP-1 receptor agonists are not associated with increased suicidality relative to DPP-4 or SGLT-2 inhibitors, while still screening for mental health risks as part of routine care.

Limitations

• Observational design cannot fully exclude residual confounding and outcome misclassification.
• Median follow-up was relatively short for rare outcomes like suicide; under-ascertainment is possible.

Future Directions

Extend analyses to longer follow-up, psychiatric subgroups, weight-loss indications, and international datasets; integrate patient-reported outcomes to improve suicidality ascertainment.