Context:

Analysis of FAERS data from 2012–2025 shows GLP-1 therapies exhibit distinct adverse event patterns across diabetes and weight-management indications, with prominent signals in metabolic, gastrointestinal, nutritional, and psychiatric domains. The study across five agents found higher reporting of several events compared with DPP-4 and SGLT2 inhibitors, including gastrointestinal symptoms, skin conditions, taste changes, and suicidal behaviors, with specific signals such as retinopathies and pancreatic neoplasms in type 2 diabetes and a range of nutritional and sensory issues in obesity. Semaglutide, dulaglutide, and exenatide stood out for certain GI and psychiatric events; liraglutide and exenatide showed more neoplasm-related reports. Clinicians are urged to monitor long-term adverse effects as GLP-1 use expands, despite limitations in spontaneous reporting data.

Dive Deeper:

• The retrospective analysis used the FAERS database and covered five commonly prescribed GLP-1s: exenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide, spanning 2012 to 2025. It encompassed 137,451 cases, with the majority linked to type 2 diabetes treatment and a substantial subset to weight control or obesity, highlighting broad off-label and on-label exposure.

• Compared with DPP-4 and SGLT2 inhibitors, GLP-1s showed markedly higher reporting for several categories of events, including skin and subcutaneous conditions (notably high odds ratios), flatulence and abdominal distension, pain in the GI tract, alopecia, taste disorders, general nutritional disorders, and suicidal or self-injurious behavior, signaling a broad safety footprint outside glycemic control.

• In type 2 diabetes, signals included retinopathies, skin and subcutaneous conditions, pancreatic neoplasms, hearing losses, and cataracts, suggesting organ-system risks beyond glucose management that may require targeted surveillance for patients on GLP-1 therapy.

• For weight control or obesity, signals encompassed general nutritional disorders, sensory abnormalities, panic attacks, suicidal behaviors, depressive disorders, immune-related conditions, and eating disorders, underscoring psychiatric and nutritional dimensions of GLP-1 exposure in this population.

• Gender-specific analyses indicated associations among female patients with menstrual irregularities, ovarian or fallopian cysts, neoplasms, and reproductive system hemorrhages, pointing to potential reproductive-system considerations in GLP-1 exposure.

• Differences among individual GLP-1s emerged, with semaglutide linked to more GI and psychiatric events, dulaglutide and exenatide to more deaths and hospitalizations, and liraglutide and exenatide to more neoplasm-related reports, while GI disorders were common across the class.

• The authors emphasize vigilance for unanticipated long-term adverse effects as millions use GLP-1s for weight management worldwide, noting limitations such as underreporting, reporting bias, incomplete data, and limited clinical detail in FAERS.