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.