Sodium-glucose co-transporter-2 inhibitors (SGLT2i) treatment and risk
of osteomyelitis: a pharmacovigilance study of the FAERS database
Abstract
Abstract Aim: we sought to estimate the association between hypoglycemic
medications especially sodium-glucose co-transporter-2 inhibitors
(SGLT2i) and osteomyelitis based on the FDA adverse event reporting
system (FAERS). Methods: Publicly available FAERS data were analyzed
using reporting odd ratio (ROR) method and Bayesian confidence
propagation neural network (BCPNN) method. The developing trend of ROR
were revealed by series of calculation based on accumulating dataset
quarter by quarter. Results: Ketoacidosis, infections, peripheral
ischemia, renal impairment, inflammation including osteomyelitis might
more likely to occur among SGLT2i users, especially canagliflozin.
Osteomyelitis and cellulitis are AEs unique to canagliflozin. Among
2,888 osteomyelitis-related reports referring to glucose lowering
medications, 2,333 cases were associated with SGLT2i, mostly with
canagliflozin counting 2,283 which generated an ROR value of 360.89 and
a lower limit of information component (IC025) of 7.79. No
BCPNN-positive signal could be generated for drugs other than insulin,
canagliflozin or drug groups excluding canagliflozin. Reports referring
to insulin could generate BCPNN-positive signals during the entire
timespan from 2004 to 2021, while BCPNN-positive signal emerged since
second quarter (Q2) of 2017, four years since the approval of SGLT2i in
Q2 of 2013, for canagliflozin and drug groups containing canagliflozin.
Conclusion: This data mining revealed that strong association between
canagliflozin treatment and developing osteomyelitis which might be a
precursor to lower extremity amputation. Further study with updated data
is needed to better characterize the risk of osteomyelitis associated
with SGLT2i.