PMID- 33895840
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20211004
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 106
IP  - 7
DP  - 2021 Jun 16
TI  - Clinical Adverse Events Associated with Sodium-Glucose Cotransporter 2 
      Inhibitors: A Meta-Analysis Involving 10 Randomized Clinical Trials and 71 553 
      Individuals.
PG  - 2133-2145
LID - 10.1210/clinem/dgab274 [doi]
AB  - CONTEXT: SGLT2is are first-line antidiabetic agents with demonstrated 
      cardiovascular benefits. Prior meta-analyses have examined adverse events (AEs) 
      associated with these drugs in general, but such knowledge needs to be updated 
      with the results of more recent trials. In addition, the occurrence of various 
      AEs with different underlying diseases is unknown. OBJECTIVE: This meta-analysis 
      aimed to investigate the occurrence of various AEs associated with sodium-glucose 
      cotransporter 2 inhibitors (SGLT2is) and to examine the level of risk of AEs in 
      patients with different underlying diseases. METHODS: We conducted a quantitative 
      meta-analysis of randomized controlled trials (RCTs) retrieved from the MEDLINE 
      and EMBASE databases and the Cochrane library on January 31, 2021. Outcomes of 
      interest included 4 overall safety outcomes (AEs) and 12 specified safety 
      outcomes. Further analyses were performed on various subgroups, which were 
      defined based on the status of diabetes mellitus (DM), atherosclerotic 
      cardiovascular disease (ASCVD), chronic kidney disease, and congestive heart 
      failure, and by the dosage of SGLT2i (high dose vs low dose). RESULTS: Our 
      analysis included 10 eligible studies with a total of 71 553 participants. The 
      meta-analysis showed that SGLT2i led to increased risks of genital infection 
      (risk ratio [RR] 3.56, 95% CI 2.84-4.46), urinary tract infection (RR 1.06, 95% 
      CI 1.00-1.12), diabetic ketoacidosis (RR 2.23, 95% CI 1.36-3.63), and volume 
      depletion (RR 1.14, 95% CI 1.06-1.23). However, the use of SGLT2i was associated 
      with reduced risks of any serious AE (RR 0.92, 95% CI 0.90-0.94), acute kidney 
      injury (AKI) (RR 0.84, 95% CI 0.77-0.91), and hyperkalemia (RR 0.84, 95% CI 
      0.72-0.99). Within the different subgroups, the risk of amputation was higher in 
      patients with ASCVD than in those without (RR 1.44 vs 0.96, P = .066). 
      CONCLUSION: The use of SGLT2is is generally safe. SGLT2is may be associated with 
      increased risks of genital infection but are protective against AKI. Of note, the 
      risk of amputation was higher in patients with ASCVD. The key to the safe use of 
      SGLT2is lies in the identification of high-risk populations and close 
      surveillance of patients after treatment.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Lin, Donna Shu-Han
AU  - Lin DS
AD  - Division of Cardiology, Department of Internal Medicine, National Taiwan 
      University Hospital, Taipei, Taiwan.
FAU - Lee, Jen-Kuang
AU  - Lee JK
AUID- ORCID: 0000-0003-3790-484X
AD  - Division of Cardiology, Department of Internal Medicine, National Taiwan 
      University Hospital, Taipei, Taiwan.
AD  - Department of Internal Medicine, National Taiwan University College of Medicine, 
      Taipei, Taiwan.
AD  - Department of Laboratory Medicine, National Taiwan University College of 
      Medicine, Taipei, Taiwan.
AD  - Cardiovascular Center, National Taiwan University Hospital, Taipei, Taiwan.
AD  - Telehealth Center, National Taiwan University Hospital, Taipei, Taiwan.
FAU - Chen, Wen-Jone
AU  - Chen WJ
AD  - Division of Cardiology, Department of Internal Medicine, National Taiwan 
      University Hospital, Taipei, Taiwan.
AD  - Cardiovascular Center, National Taiwan University Hospital, Taipei, Taiwan.
AD  - Department of Emergency, National Taiwan University College of Medicine, Taipei, 
      Taiwan.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
SB  - IM
MH  - Adult
MH  - Cardiovascular Diseases/chemically induced/epidemiology
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Diabetic Ketoacidosis/chemically induced/epidemiology
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology/etiology
MH  - Female
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects
MH  - Male
MH  - Randomized Controlled Trials as Topic
MH  - Renal Insufficiency, Chronic/chemically induced/epidemiology
MH  - Reproductive Tract Infections/chemically induced/epidemiology
MH  - Risk Factors
MH  - Sodium-Glucose Transporter 2 Inhibitors/*adverse effects
MH  - Urinary Tract Infections/chemically induced/epidemiology
OTO - NOTNLM
OT  - Sodium-glucose cotransporter 2 inhibitors
OT  - adverse events
OT  - amputation
OT  - atherosclerotic cardiovascular disease
OT  - meta-analysis
EDAT- 2021/04/26 06:00
MHDA- 2021/10/05 06:00
CRDT- 2021/04/25 20:52
PHST- 2021/03/11 00:00 [received]
PHST- 2021/04/26 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2021/04/25 20:52 [entrez]
AID - 6250093 [pii]
AID - 10.1210/clinem/dgab274 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2021 Jun 16;106(7):2133-2145. doi: 
      10.1210/clinem/dgab274.