TOPLINE:

Analysis of real-world pharmacovigilance data shows that GLP-1s demonstrate distinct adverse event patterns across indications, primarily related to metabolic, nutritional, gastrointestinal, and psychiatric disorders, with different profiles observed across treatments.

METHODOLOGY:

• With the rapid uptake of GLP-1s, postmarketing surveillance is essential to detecting safety signals not captured in clinical trials.
• Researchers conducted a retrospective analysis of the US FDA Adverse Event Reporting System (FAERS) database from 2012 to 2025, focusing on five commonly prescribed GLP-1s: exenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide.
• Subgroup analyses compared adverse event associations by indication (type 2 diabetes [T2D] vs weight control or obesity), GLP-1s vs other drugs (DPP-4 and SGLT2 inhibitors), and specific to individual GLP-1s.
• Safety signals were identified using disproportionality analyses, including reporting odds ratios (RORs) and proportional reporting ratios.

TAKEAWAY:

• The analysis included 137,451 cases involving GLP-1s, most often for T2D treatment (42,570 cases) and weight control or obesity (12,311 cases).
• Compared with DPP-4 and SGLT2 inhibitors, GLP‑1s were associated with increased reporting of several adverse events, including skin and subcutaneous conditions (ROR, 37.24); flatulence, bloating, and distension (ROR, 4.81); gastrointestinal and abdominal pain (ROR, 2.37); alopecia (ROR, 2.40); taste disorders (ROR, 4.83); general nutritional disorders (ROR, 2.61); and suicidal or self-injurious behaviors (ROR, 2.68).
• In T2D, GLP‑1 use was associated with retinopathies (ROR, 19.73), skin and subcutaneous conditions (ROR, 19.75), pancreatic neoplasms (ROR, 4.05), hearing losses (ROR, 5.45), and cataracts (ROR, 4.43).
• For weight control or obesity, GLP-1 use was associated with general nutritional disorders (ROR, 3.08), sensory abnormalities (ROR, 6.28), panic attacks and disorders (ROR, 4.63), suicidal or self-injurious behavior (ROR, 4.64), depressive disorders (ROR, 2.79), immune‑associated conditions (ROR, 3.13), and eating disorders (ROR, 2.53). Among female patients, GLP‑1s were linked to the reporting of menstrual bleeding, ovarian or fallopian cysts and neoplasms, and reproductive system hemorrhages.
• Individual GLP-1s showed varying toxicity profiles. Semaglutide was associated with more gastrointestinal and psychiatric events, dulaglutide and exenatide with more deaths and hospitalizations, and liraglutide and exenatide with more neoplasm-related reports. Gastrointestinal disorders were common across all GLP-1s.

IN PRACTICE:

“As millions of patients are taking GLP-1s for weight control and obesity treatment worldwide, clinicians should be vigilant in monitoring for unanticipated long-term adverse effects,” the authors of the study wrote.

SOURCE:

The study was led by David Stone, Departments of Oncological Sciences and Biomedical Informatics, University of Utah, Salt Lake City. It was published online in Obesity.

LIMITATIONS:

The FAERS database is limited by underreporting and differential reporting bias. Reports may be incomplete and contain missing data, which may limit the ability to establish associations between drugs and adverse events. Clinical details in the database may also be limited.

DISCLOSURES:

The study was supported by a start‑up package provided to an author from the Huntsman Cancer Institute, University of Utah. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.