A noninterventional postauthorization safety study of patients with type 2 diabetes compared the incidence of hospitalized acute liver injury (hALI) in new users of dapagliflozin and new users of comparator glucose-lowering drugs (GLDs), matched on year, age, sex, and region. Comparators included GLDs other than SGLT2 inhibitors or monotherapy with insulin, metformin, or sulfonylureas. Data sources were US Medicare (2014-2017), US HealthCore Integrated Research Database (HIRD) (2014-2019), and UK Clinical Practice Research Datalink (CPRD) (2012-2018). Incidence rates of hALI were calculated by exposure group and compared with adjusted incidence rate ratios (aIRRs) with covariate adjustment by propensity score stratification. A pooled aIRR was estimated by the Mantel-Haenszel method. The person-years of dapagliflozin and comparator exposure, respectively, was 10,315 and 91,740 in HIRD, 6,756 and 106,273 in Medicare. In CPRD, dapagliflozin person-years were unreportable due to low counts, comparator person-years were 28,950. Mean age (years) was 52 in HIRD, 70 in Medicare, and 58 in CPRD. Approximately 55% in HIRD, 53% in Medicare, and 60% in CPRD were men. In all cohorts, the observed number of hALI cases was low, and aIRRs and 95% confidence limits (CI) were wide (figure). The pooled, aIRR was 0.85 (95% CI, 0.59-1.24). This real-world study does not suggest an increased risk of hALI associated with dapagliflozin compared with other GLDs.
