Meta-analysis: Increase in suicide ‘unlikely’ among patients on GLP-1s

Key takeaways:

• A review of randomized clinical trials found 33 occurrences of suicide-related behaviors with GLP-1s vs 27 for placebo.
• Data showed no outcome differences based on diabetes status or type of GLP-1 used.

The incidence and risk for suicidality and self-harm were low for individuals given glucagon-like peptide-1 receptor agonists for obesity and diabetes, according to results of a systematic review and meta-analysis published in JAMA Psychiatry.

“While assessments of medical records and registries have not suggested increased risk of suicide or self-harm with GLP-1 receptor agonist use, these data are not ideal to answer this question,” Sean P. Heffron, MD, a preventive cardiologist at NYU Langone Health, told Healio. “We performed a meta-analysis of placebo-controlled randomized controlled trials (RCTs) to assess for a signal of risk with these medications.”

Prior research has found thread-like associations between bariatric surgery and increased suicidality, Heffron and colleagues wrote. Although GLP-1 receptor agonists have proven efficacious to treat obesity, there have been concerns on the risk for suicidality with these agents.

The researchers sought to examine the risks for suicidality and self-harm among adults with diabetes or obesity enrolled in a series of clinical trials featuring GLP-1 receptor agonists.

Their retrospective study included searches of MEDLINE, Embase, ClinicalTrials.gov and Cochrane databases from their respective points of inception through August 2023 for RCTs lasting 6 or more months or those comparing GLP-1 receptor agonists with placebo for the treatment of diabetes or obesity published in peer-reviewed journals.

From an initial pool of more than 7,200 articles, 31 were chosen featuring RCTs that included 32,357 individuals (74,740 person-years of follow up) who received GLP-1s and 27,046 who received placebo (68,095 person-years). The trials all recorded suicide and/or self-harm-related events. Two independent researchers screened the data for quality and validity and applied random-effects models for analysis, with the main review outcome as pooled incidence of either completed or attempted suicide, incidence of suicidal ideation, or self-harm.

The researchers’ analysis yielded 33 occurrences of events related to suicide among the cohort given GLP-1s (unadjusted incidence rate of 0.044 per 100 person-years) and 27 events from those given placebo (0.04 per 100 person-years) groups. Additionally, data showed no statistically significant difference in composite rate ratios among groups (rate ratio = 0.76; 95% CI, 0.48-1.21).

Heffron and colleagues also reported that data from subgroup analyses did not suggest outcome differences based on either an individual’s diabetes status or type of GLP-1 used.

The researchers said the findings “ease concerns” by showing “there is unlikely to be an increase in the very low incidence of these events” in patients on GLP-1 receptor agonists.

“Although these findings further ease concerns about these rare, catastrophic adverse effects, continued monitoring is warranted to identify potential subgroups of patients at risk for adverse events with extended and expanded use of GLP-1 receptor agonists,” Heffron told Healio.