After adjustment for confounding variables, no increased risk seen for GLP-1 receptor agonists versus DPP-4 inhibitors, SGLT-2 inhibitors
By Elana Gotkine HealthDay Reporter
MONDAY, March 3, 2025 (HealthDay News) — Glucagon-like peptide-1 (GLP-1) receptor agonists are not associated with an increased risk for suicidality compared with dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT-2) inhibitors in adjusted analyses, according to a study published online Feb. 26 in The BMJ.
Samantha B. Shapiro, from the Jewish General Hospital in Montreal, and colleagues conducted an active comparator, new user cohort study to examine whether use of GLP-1 receptor agonists is associated with an increased risk for suicidal ideation, self-harm, and suicide compared with DPP-4 inhibitor or SGLT-2 inhibitor use. The first cohort included 36,082 GLP-1 receptor agonist users and 234,028 DPP-4 inhibitor users, and the second cohort included 32,336 GLP-1 receptor agonist users and 96,212 SGLT-2 inhibitor users.
In crude analyses, the researchers found an increased incidence of suicidality with GLP-1 receptor agonist versus DPP-4 inhibitor use (crude incidence rates, 3.9 versus 1.8 per 1,000 person-years; hazard ratio, 2.08; 95 percent confidence interval, 1.83 to 2.36). After accounting for confounding factors, this estimate decreased to a null value (hazard ratio, 1.02; 95 percent confidence interval, 0.85 to 1.23). GLP-1 receptor agonist use was also associated with an increased risk for suicidality compared with SGLT-2 inhibitor use (crude incidence rates, 4.3 versus 2.7 per 1,000 person-years; hazard ratio, 1.60; 95 percent confidence interval, 1.37 to 1.87), but the correlation did not persist after accounting for confounding factors (hazard ratio, 0.91; 95 percent confidence interval, 0.73 to 1.12). When suicidal ideation, self-harm, and suicide were analyzed separately in both cohorts, the findings were similar.
“These findings should provide some reassurance with respect to the psychiatric safety of these drugs,” the authors write.
Several authors disclosed ties to the pharmaceutical industry.
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