PMID- 36865915
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230304
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Sodium-glucose co-transporter-2 inhibitor (SGLT2i) treatment and risk of 
      osteomyelitis: A pharmacovigilance study of the FAERS database.
PG  - 1110575
LID - 10.3389/fphar.2023.1110575 [doi]
LID - 1110575
AB  - Background and purpose: Several clinical trials have indicated that the use of 
      canagliflozin increases the risk of lower extremity amputation. Although the US 
      Food and Drug Administration (FDA) has withdrawn its black box warning about 
      amputation risk for canagliflozin, the risk still exists. We sought to estimate 
      the association between hypoglycemic medications, especially sodium-glucose 
      co-transporter-2 inhibitors (SGLT2is), and adverse events (AEs) before the 
      irreversible outcome of amputation as a promising early warning, based on the FDA 
      Adverse Event Reporting System (FAERS) data. Methods: Publicly available FAERS 
      data were analyzed using a reporting odds ratio (ROR) method and validated by a 
      Bayesian confidence propagation neural network (BCPNN) method. The developing 
      trend of the ROR was investigated by a series of calculations based on the 
      accumulation of data in the FAERS database quarter by quarter. Results: 
      Ketoacidosis, infection, peripheral ischemia, renal impairment, and inflammation 
      including osteomyelitis might be more likely to occur among users of SGLT2is, 
      especially canagliflozin. Osteomyelitis and cellulitis are AEs unique to 
      canagliflozin. Among 2,888 osteomyelitis-related reports referring to 
      hypoglycemic medications, 2,333 cases were associated with SGLT2is, with 
      canagliflozin accounting for 2,283 of these cases and generating an ROR value of 
      360.89 and a lower limit of information component (IC(025)) of 7.79. No 
      BCPNN-positive signal could be generated for drugs other than insulin and 
      canagliflozin. Reports suggesting that insulin could generate BCPNN-positive 
      signals span from 2004 to 2021, whereas reports with BCPNN-positive signals 
      emerged only since the second quarter (Q2) of 2017, 4 years since the approval of 
      SGLT2is in Q2 of 2013, for canagliflozin and drug groups containing 
      canagliflozin. Conclusion: This data-mining investigation revealed a strong 
      association between canagliflozin treatment and developing osteomyelitis that 
      might be a crucial forewarning to lower extremity amputation. Further studies 
      with updated data are needed to better characterize the risk of osteomyelitis 
      associated with SGLT2is.
CI  - Copyright (c) 2023 Zhao, Li, Zhang, Zhong, Yan and Qiu.
FAU - Zhao, Hui
AU  - Zhao H
AD  - Clinical Pharmacy Department, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Li, Zi-Ran
AU  - Li ZR
AD  - Clinical Pharmacy Department, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Zhang, Qian
AU  - Zhang Q
AD  - Clinical Pharmacy Department, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Zhong, Ming-Kang
AU  - Zhong MK
AD  - Clinical Pharmacy Department, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Yan, Ming-Ming
AU  - Yan MM
AD  - Clinical Pharmacy Department, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Qiu, Xiao-Yan
AU  - Qiu XY
AD  - Clinical Pharmacy Department, Huashan Hospital, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20230214
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9971937
OTO - NOTNLM
OT  - FAERS
OT  - SGLT2is
OT  - canagliflozin
OT  - diabetes mellitus
OT  - osteomyelitis
OT  - pharmacovigilance
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/03/04 06:00
MHDA- 2023/03/04 06:01
PMCR- 2023/02/14
CRDT- 2023/03/03 02:38
PHST- 2022/11/29 00:00 [received]
PHST- 2023/01/17 00:00 [accepted]
PHST- 2023/03/03 02:38 [entrez]
PHST- 2023/03/04 06:00 [pubmed]
PHST- 2023/03/04 06:01 [medline]
PHST- 2023/02/14 00:00 [pmc-release]
AID - 1110575 [pii]
AID - 10.3389/fphar.2023.1110575 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Feb 14;14:1110575. doi: 10.3389/fphar.2023.1110575. 
      eCollection 2023.