An investigation on the association between sodium glucose co‐transporter 2 inhibitors use and acute pancreatitis: A VigiBase study

Abstract

Purpose To characterize acute pancreatitis (AP) related to sodium glucose co‐transporter 2 inhibitors and to investigate this relationship through disproportionality analysis in an international pharmacovigilance database. Methods We analyzed all AP reports for canagliflozin, dapagliflozin and/or empagliflozin from the WHOs Global adverse drug reactions database VigiBase® up to July 2019. We characterized the patients, reporters, and reactions, and we present the proportional reporting ratio (PRR) and information component (IC) for each of the gliflozins. AP cases were reports containing at least one of 11 previously selected preferred terms. Gliflozin exposure was considered for all reports with at least one gliflozin as suspected/ interacting drug. Results Of the 19 834 180 individual case safety reports in VigiBase, in 600 reports containing 618 AP group reactions, gliflozins were suspected/ interacting drugs. Men were affected in 52.3% of the cases and 59.6% of the patients were in the 45–64 years age group. The reporters were in 417 cases healthcare professionals. Most of the reactions were reported for canagliflozin (59.7%), followed by empagliflozin (21%) and dapagliflozin (19.2%) and were serious (98.6%). Most of the reactions' outcomes (84% of the patients) were favorable. Ketoacidosis was frequently associated with the AP (21.3%). Significant PRR and IC were found for pancreatitis and pancreatitis acute for all three gliflozins, pancreatitis necrotizing for canagliflozin and empagliflozin and pancreatitis relapsing for empagliflozin. Conclusions Most of the AP cases were serious and with favorable outcome. We identified possible alternative causes for AP, like concomitant medication, hypertriglyceridemia, and cholelithiasis and a frequent association with ketoacidosis. We found a significant association between AP and the use of canagliflozin, dapagliflozin, and empagliflozin that would need further investigation.

A Description of Acute Renal Failure and Nephrolithiasis Associated With Sodium–Glucose Co-Transporter 2 Inhibitor Use: A VigiBase Study

“…A dose–response relationship could not be established, as variation in the number of cases per dose was probably due to the patterns of the gliflozins’ use (e.g., approximately the same number of cases for canagliflozin 100 and 300 mg, more case for dapagliflozin 10 versus 5 mg, but also more cases for empagliflozin 10 versus 25 mg). This is consistent with the dose trend of reports from another analysis that looked at the gliflozins reactions in VigiBase during the same period ( Frent et al, 2021 ).…”

Rituximab and Pyoderma Gangrenosum: An Investigation of Disproportionality Using a Systems Biology-Informed Approach in the FAERS Database

“…A 2021 pharmacovigilance study used a similar approach with respect to adjusting for the baseline risk of the outcome by stratifying by the medication indication [ 19 ]. This study estimated the risk of acute pancreatitis with sodium glucose co-transporter 2 inhibitors in Vigibase, by restricting analyses to only medicines used for diabetes mellitus, as diabetes is a potential risk factor for pancreatitis.…”

“…Our study has the same limitations of similar studies using voluntary reporting systems including under-reporting and a lack of clinical details [ 19 ]. In this study, demographic details for age, sex, duration of treatment, comorbidities, re-challenge and de-challenge were missing for many cases and this may influence the outcomes of our study.…”

“…We have combined these concepts with an additional sub-population analysis to adjust for confounding by indication. This approach may be useful in understanding the causal pathway for a potential increase in the risk of an ADR from complex immunomodulating molecules used to treat chronic autoimmune disorders such as biologic medicines [16][17][18][19][20].…”

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

“…Recently, it was shown that taking canagliflozin increases phosphate, FGF23, and PTH levels, while it decreases 1,25-dihydroxyvitamin D levels. This may have detrimental effects on bone health [ 155 , 156 , 157 , 158 , 159 ]. The rise in phosphate, FGF23, and PTH levels, as well as the reduction in 1,25-dihydroxyvitamin D levels, were all minor and occurred within the first few hours/days after treatment.…”