6D-11 - Post-Marketing Safety of Lantus Insulin Glargine and its Interchangeable Biosimilar Semglee in the United States: A Disproportionality Analysis using the FDA Adverse Event Reporting System (FAERS) Database

Background: On July 28, 2021, Semglee (insulin-glargine-yfgn) was approved by the U.S. FDA as the first interchangeable biosimilar to the reference product Lantus (insulin glargine) for treating diabetes mellitus.

Objectives: To identify reporting safety signals of Lantus and Semglee using the FDA FAERS.

Methods: This cross-sectional study utilized the FAERS to examine adverse event (AE) reports and identify safety signals of Lantus and Semglee, compared with all other drugs, within the U.S. from July 28, 2021, to September 30, 2024. We compared characteristics of age, sex, and type of reporter between Lantus and Semglee recipients (Chi-square test). The AE reports were organized into high-level group terms (HLGTs) using the Medical Dictionary for Regulatory Activities (MedDRA) hierarchy analysis. Disproportionality analysis, including reporting odds ratio (ROR) and empirical bayesian geometric mean (EBGM), was performed to detect safety signals for serious AEs, death, hospitalization, and top 6 HLGTs. Significant signals were detected if the lower boundary of 95% confidence interval (CI) of ROR or 90% of EBGM >1.0. Breslow-Day test was used to assess the homogeneity of RORs of AEs between Lantus and Semglee.

Results: A total of 19,009 and 1,412 AE reports were included for Lantus and Semglee, respectively. Semglee AE reports had a higher proportion of consumer reporters compared to Lantus (85.1% vs. 75.2%, P<.001). Lantus had higher proportions of serious AE (25.3% vs. 4.2%), death (1.3% vs. 0.2%), and hospitalization (7.4% vs. 1.4%) than Semglee (P < 0.001). No significant safety signal of serious AE, death, or hospitalization was detected for either drug. Lantus exhibited significant safety signals for device issues (ROR=1.3, 95% CI=1.2–1.4), medication errors and other product use errors and issues (ROR=2.8, 95% CI=2.7–2.9), and metabolic, nutritional, and blood gas investigations (ROR=11.7, 95% CI=11.2–12.2). Semglee had higher significant safety signals for device issues (ROR=118,7 95% CI=103.9–135.7) and medication errors and other product use errors and issues (ROR=3.4, 95% CI=3.0–3.8) but a lower safety signal for metabolic, nutritional, and blood gas investigations (ROR=3.0, 95% CI=2.3–3.9) than Lantus (Breslow-Day statistic, P< 0.001). In addition, Semglee had significant safety signals for product quality, supply, distribution, manufacturing, and quality system issues (ROR=5.4, 95% CI=4.6–6.3) and physical examination and organ system status topics (ROR=2.6, 95% CI=2.0–3.2). EBGM results were consistent with the RORs.

Conclusions: Our findings identified significant post-marketing reporting safety signals of Lantus and Semglee. Longitudinal studies are warranted to verify these detected safety signals.