SGLT2 inhibitors associated pancreatitis: signal identification through disproportionality analysis of spontaneous reports and review of case reports.

Abstract

In recent times, pancreatitis has been one of the most frequently reported adverse events for sodium-glucose cotransporter-2 (SGLT2) inhibitors. To evaluate the potential association between SGLT2 inhibitors and the risk of pancreatitis by analyzing the spontaneous reports through disproportionality analysis and reviewing case reports. A retrospective case/non-case study was conducted using spontaneous reports from the FDA Adverse Event Reporting System (FAERS), VigiBase, and the Canadian Adverse Reaction Database (CARD). Disproportionality analysis was performed by calculating the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and the Information Component (IC). In parallel, a review of case reports was conducted on SGLT2 inhibitors-induced pancreatitis. A total of 524, 510, and 40 spontaneous reports of pancreatitis suspected to be caused by SGLT2 inhibitors were identified from FAERS, VigiBase, and CARD, respectively. Through the disproportionality analysis of FAERS data, a signal was identified between the SGLT2 inhibitors and pancreatitis, with empagliflozin having highest risk [PRR = 3.9; Lower Bound (LB) ROR = 3.4; IC025 = 1.7], followed by canagliflozin [PRR = 3.6; LB ROR = 3.2; IC025 = 1.6], and dapagliflozin [PRR = 3.2; LB ROR = 2.7; IC025 = 1.4]. VigiBase and CARD data analyses reiterated the findings of FAERS. Thirteen case reports identified from a systematic literature search strengthened these findings and highlighted the importance of physical examination and laboratory parameters for the early diagnosis of pancreatitis. The current study found a potential risk of pancreatitis with the use of SGLT2 inhibitors. There is an urgent need to thoroughly investigate the same and take the necessary action to avoid or minimize the risk.