(P-177) Identification of Novel Safety Signals of sglt2 Inhibitors: A Pharmacovigilance Analysis of the Usfda and Global Adverse Event Reporting Databases

Background: Although SGLT2 inhibitors are efficacious for the treatment of type 2 diabetes, concerns remain regarding their safety.

Objectives: To identify the novel safety signals of SGLT2 inhibitors, which have not been identified to date through pre- and post-marketing surveillance.

Methods: An observational pharmacovigilance analysis was performed using data from the US FDA Adverse Event Reporting System (FAERS) and VigiBase on SGLT2 inhibitors, including canagliflozin, dapagliflozin, and empagliflozin. The study period was 29th March 2013 (the date of approval of canagliflozin by the FDA) to September 30th, 2020. Disproportionality analyses were performed by calculating the proportional reporting ratio (PRR) with an associated chi-square (𝛘2) value, lower bound of the 95% two-sided confidence interval of reporting odds ratio (LL ROR), and lower bound of the 95% two-sided confidence interval of the information component (IC025).

Results: Leaving the safety signals already identified for the SGLT2 inhibitors by FDA ,the novel signals identified by analyzing FAERS database were Cellulitis [Canagliflozin: NComb = 982, PRR = 23.65 (𝛘2 = 20801.52 ), LL ROR = 23.12, IC025 = 4.42; Dapagliflozin: NComb = 28, PRR = 2.52 (𝛘2 = 25.63), LL ROR = 1.74, IC025 = 0.71; Empagliflozin: NComb = 44, PRR = 1.68 (𝛘2 = 12.17), LL ROR = 1.25, IC025 = 0.28], Skin Ulcer [Canagliflozin: NComb = 543, PRR = 25.16 (𝛘2 = 12270.14), LL ROR = 23.62, IC025 = 4.46; Dapagliflozin: NComb = 12, PRR = 2.07 (𝛘2 = 6.65 ), LL ROR = 1.18, IC025 = 0.06; Empagliflozin: NComb = 46, PRR = 3.38 (𝛘2 = 77.03), LL ROR = 2.54, IC025 = 1.27], Pancreatitis [Canagliflozin: NComb = 272, PRR = 5.30 (𝛘2 = 945.40), LL ROR = 4.75, IC025 = 2.20; Dapagliflozin: NComb = 53, PRR = 3.93 (𝛘2 = 116.05), LL ROR = 3.02, IC025 = 1.52; Empagliflozin: NComb = 145, PRR = 4.58 (𝛘2 = 405.75 ), LL ROR = 3.92, IC025 = 1.93], Cerebral Infarction [Canagliflozin: NComb = 79, PRR = 3.37 (𝛘2 = 141.13), LL ROR = 2.82, IC025 = 1.39; Dapagliflozin: NComb = 108, PRR 18.37 (𝛘2 = 1766.19), LL ROR = 15.44 , IC025 = 3.80; Empagliflozin: NComb = 66, PRR = 4.76 (𝛘2 = 195.68), LL ROR = 3.75, IC025 = 1.84]. The event Nephrolithiasis also shows an association with Canagliflozin [NComb = 110, PRR = 3.38 (𝛘2 = 183.49), LL ROR = 2.81, IC025 = 1.45]. The analysis of global data through VigiBase reiterated the findings of FAERS.

Conclusions: This up-to-date pharmacovigilance analysis identified that the SGLT2 inhibitors are associated with serious adverse events that had not been previously identified, including cellulitis, skin ulcer, pancreatitis, and cerebral infarction. The clinical studies should be carried out to validate the identified signals.