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INTRODUCTION Disproportionality analysis is a common pharmacovigilance tool to detect safety signals of type 2 diabetes medications from spontaneous drug reporting databases. OBJECTIVE To demonstrate the impact of using the active-comparator restricted disproportionality analysis (ACR-DA), wherein the reference group is restricted to reports with a clinically appropriate active comparator. METHODS Using reports from the Food and Drug Administration Adverse Event Reporting System (FAERS), we assessed if sodium/glucose cotransporter 2 (SGLT2) inhibitors are associated with higher reporting of five potential adverse events: acute kidney injury (AKI), genitourinary tract infections (GUTI), diabetic ketoacidosis (DKA), fractures, and amputations. For each adverse event, we calculated the proportional reporting ratio (PRR) and adjusted reporting odds ratio (aROR) [95% Confidence Interval] using three types of reference groups: no SGLT2 inhibitor (background risk reference), other diabetes drugs (therapeutic class reference), and dipeptidyl peptidase 4 (DPP4) inhibitors (active comparator reference). RESULTS Based on the ACR-DA, we did not detect a safety signal for AKI (PRR 0.92 [0.81-1.04]; aROR 0.78 [95% CI 0.72-0.85]) or fractures (PRR 0.44[95% CI 0.17-1.15]; aROR 0.74 [95% CI 0.61-0.91]) associated with SGLT2 inhibitors compared to DPP4 inhibitors. However, we detected safety signals for GUTI (PRR 2.75[2.02-3.76]; aROR 2.54[2.26-2.86], DKA (PRR 63.85[39.37-103.53; aROR 91.49[70.66-118.48]), and amputations (PRR 52.60 [19.66-140.75]; aROR 22.64 [15.32-33.42]. CONCLUSIONS The use of the proposed ACR-DA analysis to detect safety signals of type 2 diabetes medications may reduce false positive safety signals through careful selection of the comparator which is expected to reduce channeling bias.