Fracture-Centred Skeletal Reporting Profiles of Glucose-Lowering Drug Classes in FAERS and JADER: Cross-Database and Regional Reporting-Context Analyses.

AIMS: To characterise fracture-centred skeletal adverse-event reporting across nine glucose-lowering drug classes and test whether regional differences persist after separating Japan from non-Japan Asian reporting contexts.

MATERIALS AND

METHODS

We analysed FAERS and JADER reports, with fracture as the primary endpoint and reporting frequency per 10 000 mapped suspect reports. FAERS older age was harmonised to ≥ 60 years, with ≥ 65 and ≥ 70-year sensitivity analyses. Regional analyses separated Western, Japan, and non-Japan Asia; class-specific reporting odds were adjusted for age, sex, calendar year, and reporter type. Disproportionality analyses were supplementary.

RESULTS

The study included 15 473 015 FAERS and 1 037 161 JADER reports, including 202 881 and 10 678 fractures. Using final deduplicated FAERS denominators, fracture reporting was highest for insulin (126.08/10000), DPP-4 inhibitors (111.03) and sulfonylureas (103.76), whereas thiazolidinediones (152.54), SGLT2 inhibitors (115.14) and GLP-1 receptor agonists (112.15) were most prominent in JADER. Age was unavailable in 44.9% of unique FAERS suspect reports, but findings were stable across age thresholds. Japan accounted for 83.0%-92.9% of total-Asian fractures for thiazolidinediones, GLP-1 receptor agonists, SGLT2 inhibitors and DPP-4 inhibitors; corresponding non-Japan Asian RFRs were not clearly elevated. Insulin remained higher after excluding Japan (RFR 1.96, 95% CI 1.57-2.45). No class met FDR-positive fracture disproportionality criteria.

CONCLUSIONS

Skeletal reporting profiles varied by drug class, database, and reporting context. Apparent total-Asian elevations for several classes were predominantly Japan-driven and should not be interpreted as patient-level Asian fracture risk.