Compared to DPP-4 inhibitors, SGLT2 inhibitors were associated with higher reporting of diabetic ketoacidosis (aROR 91.49; 95% CI 70.66-118.48) and amputations, but not acute kidney injury.
Observational
Does the use of active-comparator restricted disproportionality analysis impact the detection of safety signals for SGLT2 inhibitors in pharmacovigilance databases?
Using an active-comparator restricted disproportionality analysis in pharmacovigilance databases may reduce false-positive safety signals by mitigating channeling bias.
Odds Ratio: 0.78 (95% CI 0.72–0.85)
AIMS: Disproportionality analysis is a common pharmacovigilance tool to detect safety signals of type 2 diabetes medications from spontaneous drug reporting databases. The aim was to demonstrate the impact of using 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, we assessed if sodium/glucose cotransporter 2 (SGLT2) inhibitors are associated with higher reporting of 5 potential adverse events: acute kidney injury, genitourinary tract infections, diabetic ketoacidosis, fractures, and amputations. For each adverse event, we calculated the proportional reporting ratio (PRR) and adjusted reporting odds ratio (aROR 95% confidence interval, CI) using 3 types of reference groups: no SGLT2 inhibitor (background risk reference), other diabetes drugs (therapeutic class reference), and dipeptidyl peptidase 4 inhibitors (active comparator reference). RESULTS: Based on ACR-DA, we did not detect a safety signal for acute kidney injury (PRR 0.92 0.81-1.04; aROR 0.78 95% CI 0.72-0.85) or fractures (PRR 0.4495% CI 0.17-1.15; aROR 0.74 95% CI 0.61-0.91) associated with SGLT2 inhibitors compared to dipeptidyl peptidase 4 inhibitors. However, we detected safety signals for genitourinary tract infections (PRR 2.752.02-3.76; aROR 2.542.26-2.86, diabetic ketoacidosis (PRR 63.8539.37-103.53; aROR 91.49[70.66-118.48), and amputations (PRR 52.60 19.66-140.75; aROR 22.64 15.32-33.42. CONCLUSION: The use of the proposed ACR-DA 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 channelling bias.
Alkabbani et al. (Wed,) conducted a observational in Type 2 diabetes. Sodium/glucose cotransporter 2 (SGLT2) inhibitors vs. Dipeptidyl peptidase 4 (DPP-4) inhibitors was evaluated on Acute kidney injury (aROR 0.78, 95% CI 0.72-0.85). Compared to DPP-4 inhibitors, SGLT2 inhibitors were associated with higher reporting of diabetic ketoacidosis (aROR 91.49; 95% CI 70.66-118.48) and amputations, but not acute kidney injury.