PMID- 31616297
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 10
DP  - 2019
TI  - Appraisal of Non-Cardiovascular Safety for Sodium-Glucose Co-Transporter 2 
      Inhibitors: A Systematic Review and Meta-Analysis of Placebo-Controlled 
      Randomized Clinical Trials.
PG  - 1066
LID - 10.3389/fphar.2019.01066 [doi]
LID - 1066
AB  - Background: Whereas the cardiovascular safety of sodium-glucose co-transporter 2 
      (SGLT2) inhibitors has been well reported, there is limited data from controlled 
      clinical trials regarding the non-cardiovascular safety. This was the focus of 
      our study. Methods and Findings: We systematically searched MEDLINE, EMBASE, and 
      Cochrane Library (5(th) Sep 2018) for randomized controlled trials (RCTs) that 
      reported safety data for SGLT2 inhibitors and placebo. Relative risks (RRs) and 
      their 95% confidence intervals (CIs) were pooled using random-effects models. 
      Seventy RCTs (83 studies enrolling 36,958 patients in 78 publications) were 
      identified. SGLT2 inhibitors were associated with a lower risk of serious adverse 
      events (RR 0.90, 95% CI 0.86 to 0.94, P < 0.001), death (RR 0.78, 95% CI 0.64 to 
      0.94, P < 0.05), gastroenteritis (RR 0.38, 95% CI 0.20 to 0.72, P < 0.05), 
      arthralgia (RR 0.72, 95% CI 0.54 to 0.96, P < 0.05), hypertension (RR 0.61, 95% 
      CI 0.50 to 0.75, P < 0.001), and edema/peripheral edema (RR 0.49, 95% CI 0.33 to 
      0.72, P < 0.001) compared to placebo. SGLT2 inhibitors were associated with 
      higher risk of infections compared to placebo (RR 1.27, 95% CI 1.17 to 1.37, P < 
      0.001), especially for genital mycotic infection (GMI) (RR 3.71, 95% CI 3.19 to 
      4.32, P < 0.001). Other significant effects were observed for osmotic 
      diuresis-related AEs (RR 2.73, 95% CI 2.20 to 3.40, P < 0.001), volume-related 
      AEs (RR 1.26, 95% CI 1.08 to 1.46, P < 0.05), renal-related AEs (RR 1.36, 95% CI 
      1.02 to 1.80, P < 0.05), hypoglycemia (RR 1.18, 95% CI 1.10 to 1.26, P < 0.001), 
      and increased blood ketone bodies (RR 2.00, 95% CI 1.01 to 3.97, P < 0.05). 
      Subgroup and sensitivity analyses strengthened the robustness of primary results. 
      Conclusion: Results from RCTs confirmed lower risk of death, serious adverse 
      events, hypertension, and edema associated with type 2 diabetes mellitus (T2DM) 
      patients treated with SGLT2 inhibitors when compared with placebo. The use of 
      SGLT2 inhibitors were associated with higher risk of infection, osmotic diuresis, 
      volume depletion effects, renal related AEs, and higher blood ketone bodies when 
      compared with placebo.
CI  - Copyright (c) 2019 Shi, Li, Shen, Zhang, Jiang, Hu, Liu, Gu, Ma and Lin.
FAU - Shi, Fang-Hong
AU  - Shi FH
AD  - Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Li, Hao
AU  - Li H
AD  - Department of Pharmacy, Shanghai Children's Medical Center, School of Medicine, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Shen, Long
AU  - Shen L
AD  - Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Zhang, Zhen
AU  - Zhang Z
AD  - Pharmacy Department, Memorial Healthcare System, Hollywood, FL, United States.
FAU - Jiang, Yi-Hong
AU  - Jiang YH
AD  - Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Hu, Yao-Min
AU  - Hu YM
AD  - Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Liu, Xiao-Yan
AU  - Liu XY
AD  - Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Gu, Zhi-Chun
AU  - Gu ZC
AD  - Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Ma, Jing
AU  - Ma J
AD  - Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Lin, Hou-Wen
AU  - Lin HW
AD  - Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
LA  - eng
PT  - Systematic Review
DEP - 20190919
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6764217
OTO - NOTNLM
OT  - meta-analysis
OT  - non-cardiovascular safety
OT  - randomized controlled trials
OT  - sodium-glucose co-transporter 2 inhibitors
OT  - systematic review
OT  - type 2 diabetes mellitus
EDAT- 2019/10/17 06:00
MHDA- 2019/10/17 06:01
PMCR- 2019/09/19
CRDT- 2019/10/17 06:00
PHST- 2019/02/15 00:00 [received]
PHST- 2019/08/21 00:00 [accepted]
PHST- 2019/10/17 06:00 [entrez]
PHST- 2019/10/17 06:00 [pubmed]
PHST- 2019/10/17 06:01 [medline]
PHST- 2019/09/19 00:00 [pmc-release]
AID - 10.3389/fphar.2019.01066 [doi]
PST - epublish
SO  - Front Pharmacol. 2019 Sep 19;10:1066. doi: 10.3389/fphar.2019.01066. eCollection 
      2019.