GLP-1s Not Linked With Higher Suicide Risk Compared to Other Diabetes Drugs
A new study found that GLP-1s were not associated with an increased risk of suicidal ideation, self-harm, or suicide compared to DPP-4 and SGLT-2 inhibitors.
Glucagon-like peptide-1 (GLP-1) receptor agonists were not associated with an increased risk of suicide compared to dipeptidyl peptidase-4 (DPP-4) or sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with type 2 diabetes (T2D), according to data published in BMJ.1 Authors of the study said the findings provide reassurance about the medication’s psychiatric safety.
GLP-1s Not Linked With Higher Suicide Risk Compared to Other Diabetes Drugs / K KStock - stock.adobe.com
GLP-1s have become a significantly popular class of medication, with 1 in 8 adults in the United States reporting having ever taken one. About 62% of those said they took a GLP-1 for a chronic condition like diabetes or heart disease, while 4 in 10 said they took them to lose weight.2 This surge in use has resulted in drug shortages that negatively impact patients. Just recently, the FDA announced that the shortage of semaglutide was resolved after being in shortage since 2022.3
READ MORE: Glycemic Control Among Patients With Diabetes Worsened Over Past Decade
“The GLP-1 receptor agonist drug class is widely prescribed to manage T2D,” the authors said. “In large trials of cardiovascular outcomes, GLP-1 receptor agonists were highly effective in achieving glycemic control, showing beneficial cardiorenal effects and reducing all-cause mortality. Despite these benefits, recent reports linking GLP-1 receptor agonists to suicidal ideation and self-harm have raised significant concerns.”
Investigators from the Lady Davis Institute and McGill University conducted a study to examine whether the use of GLP-1s is associated with an increased risk of suicidal ideation, self-harm, and suicide among patients with T2D compared to DPP-4 and SGLT-2 inhibitors. Data for the study was gathered from the UK Clinical Practice Research Datalink, which is linked to the Hospital Episode Statistics Admitted Patient Care and Office for National Statistics Death Registration databases.
For the study, investigators created 2 cohorts. The first cohort included patients who started and continued a GLP-1 or DPP-4 inhibitor for the first time between January 2007 and December 2020. The second cohort included patients who started and continued on a GLP-1 or an SGLT-2 inhibitor for the first time between January 2013 and December 2020. Patients were excluded from the study if they were under 18 years of age, had less than 1 year of medical history in the database, did not have T2D, had contraindications, or had concurrent prescriptions for a GLP-1 and the comparator drug.
The study found that, among 36082 GLP-1 users, there were 301 suicidality events over 77377 person years, compared to 1087 events over 599271 person years among DPP-4 inhibitor users. Although there was an increased risk for GLP-1 users, there was no association after weighing for confounders, including age, body mass index, diabetes severity, and mental health disorders.
In the GLP-1 and SGLT-2 inhibitor group, there were 240 suicidality events over 55620 person years among 32336 GLP-1 users, compared to 454 events over 168384 person years among 96212 SGLT-2 inhibitor users. Similarly to the GLP-1 and DPP-4 group, there was an increased risk for GLP-1 users, but there was no association after weighing for confounders.
Study limitations include the possibility of residual confounding, that prescriptions written by specialists were not included, that identified self-harm was limited by using hospital admission events, and that some secondary analyses generated wide confidence intervals.
“The absence of an independent association between GLP-1 receptor agonists and suicidality suggests that the effects of these drugs on the hypothalamic-pituitary-adrenal axis, sudden weight loss, or brain derived neurotrophic factor dysregulation are not sufficient to induce suicidal ideation, self-harm, or suicide,” the authors concluded. “Although these biological mechanisms may contribute to the complex interplay of factors influencing suicidality, they do not seem to act independently in causing such outcomes in GLP-1 receptor agonist users.”
READ MORE: Diabetes Resource Center
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References
1. Shapiro SB, Yin H, Yu OHY, et al. Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study BMJ 2025; 388 :e080679 doi:10.1136/bmj-2024-080679
2. KFF Health Tracking Poll May 2024: The Public’s Use and Views of GLP-1 Drugs. Report. KFF. May 10, 2024. Accessed February 28, 2025. https://www.kff.org/health-costs/poll-finding/kff-health-tracking-poll-may-2024-the-publics-use-and-views-of-glp-1-drugs/
3. FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. News Release. FDA. February 21, 2025. Accessed February 28, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize
Glycemic Control Among Patients With Diabetes Worsened Over Past Decade
February 27th 2025Authors of a research letter published in JAMA said that the decrease in glycemic control may be due to consequences of the COVID-19 pandemic, such as sedentary behavior and increased mental health stressors.
