In conclusion, based on FAERS data, diabetes is a predominant risk for
lower extremity amputation, and most antidiabetic drugs demonstrated
curative affects on this prognosis, while SGLT2i was less effective on
this issue. Ketoacidosis, infections, peripheral ischemia, renal
impairment, inflammation might more likely to occur among SGLT2i users,
especially canagliflozin. Osteomyelitis and cellulitis are AEs unique to
canagliflozin, and therefore intensively discussed. ROR,
IC025 as well as q-ROR tendency of
canagliflozin-osteomyelitis pair were significantly different from those
generated by insulin-osteomyelitis pair, and there was no positive
signal for hypoglycemic drugs other than canagliflozin and insulin. Our
findings strongly indicated that canagliflozin treatment increasing the
risk of developing osteomyelitis from the very early stage, prior to the
advanced stage when insulin was prescribed. It is worth investigating
whether SGLT2i can result in developing osteomyelitis also in patients
without diabetes, and association between osteomyelitis and the lately
approved SGLT2i, whenever there are enough reports. Further studies are
needed to characterize a better understanding the association between
SGLT2i treatment and risk of osteomyelitis.
Acknowledgements: We would like to thank the pharmacist
Shu-Shan Wu of University of Nebraska Medical Center College of
Pharmacy, Omaha, USA for preparing the raw data from FAERS database, and
all the co-workers of Pharmacy Department, Huashan Hospital, Fudan
University, Shanghai, China for their supporting which enables this
effort.
Conflict of interest: The authors have stated explicitly that
there are no conflicts of interest in connection with this article.
Author contribution: Xiao-Yan Qiu and
Ming-Kang Zhong designed the
study; Ming-Ming Yan, Hui Zhao conducted the study; Zi-Ran Li and Qian
Zhang contributed to the formation of figures and Jun-Wei Chow
contributed to improve the analytical method. Ming-Ming Yan and Hui Zhao
contributed equally to the manuscript. Xiao-Yan Qiu and Ming-Kang Zhong
are co-corresponding authors. Xiao-Yan Qiu is the lead contact author.
Funding: This study was sponsored by 2020 Shanghai ”Rising
Stars of Medical Talent” Youth Development Program-Clinical Pharmacist
Program (SHWSRS (2021) 099).