TY - JOUR
T1 - Risk of amputation associated with sodium-glucose co-transporter 2 inhibitors
T2 - A meta-analysis of five randomized controlled trials
AU - Miyashita, Satoshi
AU - Kuno, Toshiki
AU - Takagi, Hisato
AU - Sugiyama, Takehiro
AU - Ando, Tomo
AU - Valentin, Nelson
AU - Shimada, Yuichi J.
AU - Kodaira, Masaki
AU - Numasawa, Yohei
AU - Kanei, Yumiko
AU - Bangalore, Sripal
N1 - Funding Information:
Dr. Shimada was supported in part by unrestricted grants from the American Heart Association National Clinical and Population Research Award and Career Development Award, Honjo International Scholarship Foundation, and Korea Institute of Oriental Medicine. The funding organizations did not have any role in the study design, collection, analysis, or interpretation of data, in writing of the manuscript, or in the decision to submit the article for publication. The researchers were independent from the funding organizations.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/5
Y1 - 2020/5
N2 - Amputation has been known to be a rare adverse event of sodium glucose co-transporter-2 (SGLT2) inhibitors. It remains unclear whether the SGLT2 inhibitor as a class or specific categories of the SGLT2 inhibitors are linked with an increased risk of amputation. The objective of this meta-analysis was to investigate the association between the amputation risk and the use of SGLT2 inhibitors. The main outcome measure was the risk of amputation. Multiple databases were searched up to February 2020 and data extraction was performed. Inclusion criteria were randomized controlled trials (RCTs) which reported risk of amputation with SGLT2 inhibitors over non-SGLT2 inhibitors or placebo. The risk of bias was assessed by Cochrane bias tool. The initial search yielded 1,873 citations and a total of five RCTs were included in the meta-analysis. The five included studies evaluated a total of 39,067 patients with diabetes mellitus, including 21,395 patients on SGLT2 inhibitors. The incidence rate of amputation ranged from 0.36 to 3.18% in the SGLT2 inhibitor group and from 0% to 2.87% in the control group. Follow up duration ranged from 24 weeks to 4.2 years. Use of SGLT2 inhibitors was not associated with significant increase in the risk of amputation as compared with controls (OR: 1.31, 95% CI: 0.92–1.87, I2 = 75%). Subgroup analysis showed that neither canagliflozin, empagliflozin, nor dapagliflozin was associated with increased risk of amputation. In conclusion, our meta-analysis showed that neither canagliflozin nor other SGLT2 inhibitors increase the risk of amputation.
AB - Amputation has been known to be a rare adverse event of sodium glucose co-transporter-2 (SGLT2) inhibitors. It remains unclear whether the SGLT2 inhibitor as a class or specific categories of the SGLT2 inhibitors are linked with an increased risk of amputation. The objective of this meta-analysis was to investigate the association between the amputation risk and the use of SGLT2 inhibitors. The main outcome measure was the risk of amputation. Multiple databases were searched up to February 2020 and data extraction was performed. Inclusion criteria were randomized controlled trials (RCTs) which reported risk of amputation with SGLT2 inhibitors over non-SGLT2 inhibitors or placebo. The risk of bias was assessed by Cochrane bias tool. The initial search yielded 1,873 citations and a total of five RCTs were included in the meta-analysis. The five included studies evaluated a total of 39,067 patients with diabetes mellitus, including 21,395 patients on SGLT2 inhibitors. The incidence rate of amputation ranged from 0.36 to 3.18% in the SGLT2 inhibitor group and from 0% to 2.87% in the control group. Follow up duration ranged from 24 weeks to 4.2 years. Use of SGLT2 inhibitors was not associated with significant increase in the risk of amputation as compared with controls (OR: 1.31, 95% CI: 0.92–1.87, I2 = 75%). Subgroup analysis showed that neither canagliflozin, empagliflozin, nor dapagliflozin was associated with increased risk of amputation. In conclusion, our meta-analysis showed that neither canagliflozin nor other SGLT2 inhibitors increase the risk of amputation.
KW - Amputations
KW - Diabetes mellitus
KW - Sodium-glucose co-transporter 2 inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85083053229&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083053229&partnerID=8YFLogxK
U2 - 10.1016/j.diabres.2020.108136
DO - 10.1016/j.diabres.2020.108136
M3 - Article
C2 - 32272190
AN - SCOPUS:85083053229
SN - 0168-8227
VL - 163
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
M1 - 108136
ER -