PMID- 32841351
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20210216
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 105
IP  - 11
DP  - 2020 Nov 1
TI  - Clinical Adverse Events of High-Dose vs Low-Dose Sodium-Glucose Cotransporter 2 
      Inhibitors in Type 2 Diabetes: A Meta-Analysis of 51 Randomized Clinical Trials.
LID - dgaa586 [pii]
LID - 10.1210/clinem/dgaa586 [doi]
AB  - AIMS: The aims of this work are to assess the clinical adverse events (AEs) of 
      high-dose vs low-dose sodium-glucose cotransporter 2 inhibitors (SGLT2 
      inhibitors) in patients with type 2 diabetes mellitus (T2DM). METHODS: We 
      searched MEDLINE, EMBASE, and Cochrane Library from January 1, 2006 to March 10, 
      2020, for identifying eligible randomized clinical trials (RCTs) that reported 
      AEs by high-dose and low-dose SGLT2 inhibitors in T2DM patients. Random-effects 
      models was used to obtain summary relative risks (RRs) with associated 95% CIs. 
      Prespecified subgroup analyses according to individual SGLT2 inhibitors and 
      follow-up duration, and leave-one-out sensitivity analysis were conducted. 
      RESULTS: A total of 51 RCTs involving 24 371 patients (12 208 received high-dose 
      and 12 163 received low-dose SGLT2 inhibitors) were included. Overall, the 
      heterogeneity among included studies was relatively low (I2 < 50% for each 
      outcome). No significant differences between high-dose and low-dose SGLT2 
      inhibitors were observed for overall safety (including any AEs, serious AEs, AEs 
      leading to discontinuation, and death) and specified safety (including infections 
      and infestations, musculoskeletal disorders, gastrointestinal disorders, osmotic 
      diuresis-related AEs, volume-related AEs, renal-related AEs, and metabolism and 
      nutrition), except for a mild increase in risk for AEs related to study drugs 
      (RR: 1.08; 95% CI, 1.01-1.16) that mainly derived from canagliflozin (RR: 1.17; 
      95% CI, 1.05-1.30). Subgroup analyses were consistent with the primary outcomes. 
      CONCLUSIONS: This study provided substantial evidence that AEs of SGLT2 
      inhibitors were not dose related.
CI  - (c) Endocrine Society 2020. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Shi, Fang-Hong
AU  - Shi FH
AD  - Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong 
      University, Shanghai, China.
FAU - Li, Hao
AU  - Li H
AD  - Department of Pharmacy, Shanghai Children's Medical Center, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
AD  - Clinical Research Center, Shanghai Children's Medical Center, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Yue, Jiang
AU  - Yue J
AD  - Department of Endocrinology, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai, China.
FAU - Jiang, Yi-Hong
AU  - Jiang YH
AD  - Department of Endocrinology, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai, China.
FAU - Gu, Zhi-Chun
AU  - Gu ZC
AD  - Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong 
      University, Shanghai, China.
FAU - Ma, Jing
AU  - Ma J
AD  - Department of Endocrinology, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai, China.
FAU - Lin, Hou-Wen
AU  - Lin HW
AD  - Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong 
      University, Shanghai, China.
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  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/*adverse 
      effects/therapeutic use
OTO - NOTNLM
OT  - adverse events
OT  - clinical approved dose
OT  - dose-related
OT  - meta-analysis
OT  - sodium-glucose cotransporter 2 inhibitors
OT  - type 2 diabetes mellitus
EDAT- 2020/08/26 06:00
MHDA- 2021/02/17 06:00
CRDT- 2020/08/26 06:00
PHST- 2020/06/21 00:00 [received]
PHST- 2020/08/20 00:00 [accepted]
PHST- 2020/08/26 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2020/08/26 06:00 [entrez]
AID - 5897042 [pii]
AID - 10.1210/clinem/dgaa586 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2020 Nov 1;105(11):dgaa586. doi: 10.1210/clinem/dgaa586.