Mortality and Serious Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System

• Published in: Curēus (Palo Alto, CA) CA), 2024-08, Vol.16 (8), p.e65989
• Main Authors: Bhattacharyya, Mehul, Miller, Larry E, Miller, Anna L, Bhattacharyya, Ruemon
• Format: Article
• Language: English
• Subjects: CFR; Clinical trials; Diabetes; Disease; Drug dosages; Endocrinology/Diabetes/Metabolism; Epidemiology/Public Health; FDA approval; Gastrointestinal surgery; GLP-1 receptor agonists; Glucagon; Insulin; Mortality; Obesity; Overweight; Peptides; Pharmacovigilance; Surveillance; Trends; Weight control
• ISSN: 2168-8184; 2168-8184
• DOI: 10.7759/cureus.65989

Purpose Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an increasingly prevalent class of drugs for managing overweight/obesity and type 2 diabetes mellitus. Postmarket surveillance is essential for characterizing their risk profiles in real-world patient populations as clinical use increases. This study investigated the association of GLP-1RAs with mortality and serious adverse events (AEs) reported to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods A disproportionality analysis was conducted utilizing FAERS data from Q2 2005 to Q1 2024 to identify AEs listing an approved GLP-1RA as the primary suspect drug. The reporting odds ratio (ROR) was calculated for mortality and serious AEs associated with each GLP-1RA compared to the combined group of all other GLP-1RAs. A signal of disproportionate reporting indicating a potential safety concern was defined as a lower bound of the 95% CI for the ROR exceeding 1.0. Results The analysis identified 287,201 AEs associated with GLP-1RAs during the study period. Disproportionality analyses revealed statistically significant elevated signals for mortality with the earliest approved GLP-1RAs: Byetta (ROR = 2.20, 95% CI: 2.06-2.34) and Victoza (ROR = 2.12, 95% CI: 1.98-2.28). Significant elevated signals for serious AEs were identified with the semaglutide products Ozempic (ROR = 2.77, 95% CI: 2.69-2.85), Rybelsus (ROR = 2.42, 95% CI: 2.26-2.60), and Wegovy (ROR = 1.30, 95% CI: 1.22-1.39); the liraglutide products Victoza (ROR = 2.10, 95% CI: 2.04-2.15) and Saxenda (ROR = 2.21, 95% CI: 2.09-2.33); and Byetta (ROR = 1.11, 95% CI: 1.08-1.14) compared to other GLP-1RAs. The newer GLP-1RAs were associated with a higher proportion of serious AEs reported in younger patients (p < 0.001) and females (p < 0.001). Conclusion This pharmacovigilance study utilizing the FAERS database identified potential safety signals of increased mortality and serious AE reporting associated with certain GLP-1RAs, particularly the earlier approved liraglutide agents Byetta and Victoza. These findings highlight the importance of proactive postmarket surveillance to characterize the real-world safety profiles of individual GLP-1RA drugs.