Research on Adverse Drug Reactions of GLP-1RA Based on FAERS Database

OBJECTIVE To analyze and mine adverse drug reaction(ADR) signals and off-label safety risks of 6 glucagon-like peptide-1 receptor agonists(GLP-1RA) using the U.S. FDA adverse event reporting system(FAERS), thereby providing a reference for the rational use of clinical medication.

METHODS Using the online tool Open Vigil 2.1 to retrieve adverse drug event(ADE) reports submitted to the U.S. FAERS database from the first quarter of 2004 to the third quarter of 2023. The ADEs were coded with the preferred terms(PT) from the Medical Dictionary for Regulatory Activities(MedDRA) and subsequently translated into Chinese. Signal mining was conducted using the proportional imbalance method so as to screen and analyze the ADR signals.

RESULTS A total of 61495, 24553, 53846, 1985, 20330, and 18961 ADE reports were retrieved for exenatide, liraglutide, dulaglutide, lixisenatide, tirzepatide, and semaglutide, respectively. Female patients accounts for a higher proportion than male patients. The primary reporting countries included the United States, the United Kingdom, France, and Japan. The ADR signal with the highest number of cases for exenatide and lixisenatide was hyperglycemia; for liraglutide and semaglutide, it was nausea; and for tirzepatide and dulaglutide, it was injection site pain. In addition, the signal intensity of liraglutide induced pancreatitis was the highest among the six drugs(PRR=25.149). The gastrointestinal ADRs with lower case detection rate were epigastric pain and abdominal discomfort, and lixisenatide had the lowest gastrointestinal ADR detection rate.

CONCLUSION Utilizing the FAERS database to retrieve ADR signals of 6 GLP-1RAs since their market approval can provide a basis for clinical medication safety. To improve patients’ medication compliance, special attention should be paid to gastrointestinal adverse reactions, while also closely monitoring new risk signals, such as hyperglycemia and weight gain.