Hypoglycemia following the use of glucagon-like peptide-1 receptor agonists: a real-world analysis of post-marketing surveillance data

BACKGROUND: Recent evidence has emerged concerning hypoglycemia following the application of glucagon-like peptide-1 receptor agonists (GLP-1RAs). Nevertheless, few real-world investigations have been performed to determine the clinical characteristics, onset, and outcomes of hypoglycemia associated with different GLP-1RAs. This study aimed to compare and assess the relationship between various GLP-1RAs and hypoglycemia in a large population based on updated data from the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: Bayesian and disproportionality analyses were applied to data mining in order to investigate suspected cases of hypoglycemia following various GLP-1RAs using the FAERS data between January 2004 and September 2020. We also evaluated the onset time, fatality risks, and hospitalization proportions of GLP-1RA-related hypoglycemia. RESULTS: We identified 1,164 GLP-1RA-associated hypoglycemia cases, which seemed to affect more middle-aged patients than elderly ones. Also, females were more affected than males. Lixisenatide demonstrated a stronger association with hypoglycemia compared to other GLP-1RAs, according to the highest reporting odds ratio (ROR) (28.03, 95% confidence interval =15.92, 49.32), empirical Bayes geometric mean [26.00, 95% confidence interval (CI): 16.20], and proportional reporting ratio (PRR) (26.01, χ(2)=313.37). The median time to hypoglycemia onset was 5 days (interquartile range, 0–67.75 days) following GLP-1RA treatment. In general, GLP-1RA-associated hypoglycemia resulted in fatality and hospitalization proportions of 3.53% and 56.08%, respectively. CONCLUSIONS: By analyzing the FAERS data, we outlined the association between hypoglycemia and different GLP-1RAs in greater detail in terms of clinical features, onset, and outcomes. Among all six GLP-1RAs, lixisenatide demonstrated the strongest association with hypoglycemia while no relationship between albiglutide and hypoglycemia was observed. Attention should be given to GLP-1RAs when used in patients with high risks of hypoglycemia.