Details
The U.S. Food and Drug Administration (FDA) initiated this study in the Sentinel System to evaluate a potential association between use of glucagon-like peptide‑1 receptor agonists (GLP‑1 RAs) and intentional self-harm. FDA began investigating an association between GLP‑1 RAs and suicidal ideation and behavior (SI/B) in July 2023 upon learning of post-marketing reports of (SI/B) in patients taking GLP-1 RAs. FDA performed a preliminary review of clinical trials and postmarketing data, including observational studies and case reports, and publicly reported those findings in its January 2024 Drug Safety Communication. FDA conducted analyses using U.S. claims data to assess the risk of intentional self-harm following new use of GLP-1 RAs, in the Sentinel Distributed Database, to further evaluate the safety signal. FDA conducted both comparative and descriptive analyses with Sentinel System data.
In comparative analyses, the primary analyses compared the risk of intentional self-harm between new users of GLP-1 RA and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and separately between GLP-1 RA and dipeptidyl peptidase-4 (DPP-4) inhibitors, in a large population of commercially and privately insured individuals aged 18 years or older with type 2 diabetes. The adjusted incidence rates of intentional self-harm per 1,000 person‑years were 1.13 events for GLP‑1 RAs, 1.22 events for SGLT‑2 inhibitors, and 1.37 events for DPP‑4 inhibitors. Adjusted hazard ratios (HR) did not show an increased risk among GLP‑1 RA users compared with either comparator (GLP‑1 RAs vs. SGLT‑2 inhibitors: HR 0.93; 95% CI 0.81, 1.08; GLP‑1 RAs vs DPP‑4 inhibitors: HR 0.94; 95% CI 0.82, 1.07). Similarly, FDA did not find an increased risk in the subgroup of patients with both type 2 diabetes mellitus and obesity.
FDA also conducted a descriptive analysis among patients aged 18 years or older with obesity and without evidence of diabetes or pregnancy to evaluate the occurrence of intentional self-harm following incident use of GLP‑1 RAs or other weight‑loss agents.
Results from the Sentinel comparative analyses supported FDA’s investigation of the safety concern and informed FDA’s evaluation of GLP-1 RAs and SI/B. Considering the totality of the evidence, including results from the Sentinel analyses, an internal meta-analysis of clinical trials across GLP-1 RA drug development programs, as well as a review of published studies, FDA issued a Drug Safety Communication summarizing its findings of no increased risk of SI/B associated with the use of GLP-1 RA medications. FDA requested removal of the warning for suicidal behavior and ideation from the labeling of Saxenda (liraglutide), Wegovy (semaglutide), and Zepbound (tirzepatide) on January 13, 2026.