Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular disease, death and safety outcomes in type 2 diabetes - A systematic review
Author(s)
Type
Journal Article
Abstract
Aim
Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes.
Methods
MEDLINE, EMBASE, the Cochrane Library and regulatory databases were systematically searched for data from randomized clinical trials that included reporting of cardiovascular events, deaths or safety outcomes. We used fixed effects models and inverse variance weighting to calculate relative risks with the 95% confidence intervals.
Results
The analyses included data from 82 trials, four overviews and six regulatory reports and there were 1,968 major cardiovascular events identified for analysis. Patients randomly assigned to SGLT2 had lower risks of major cardiovascular events (RR 0.85, 95%CI 0.77–0.93), heart failure (RR 0.67, 95%CI 0.55–0.80), all-cause death (RR 0.79, 95%CI 0.70–0.88) and serious decline in kidney function (RR 0.59, 0.49–0.71). Significant adverse effects were observed for genital infections (RR 3.06, 95%CI 2.73–4.43), volume depletion events (RR 1.24, 95%CI 1.07–1.43) and amputation (RR 1.44 95%CI 1.13–1.83). There was a high likelihood of differences in the associations of the individual compounds with cardiovascular death, hypoglycaemia and amputation (all I2 > 80%) and a moderate likelihood of differences in the associations with non-fatal stroke, all-cause death, urinary tract infection and fracture (all I2 > 30%).
Conclusion
There are strong overall associations of SGLT2 inhibition with protection against major cardiovascular events, heart failure, serious decline in kidney function and all-cause death. SGLT2 inhibitors were also associated with infections, volume depletion effects and amputation. Some associations appear to differ between compounds.
Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes.
Methods
MEDLINE, EMBASE, the Cochrane Library and regulatory databases were systematically searched for data from randomized clinical trials that included reporting of cardiovascular events, deaths or safety outcomes. We used fixed effects models and inverse variance weighting to calculate relative risks with the 95% confidence intervals.
Results
The analyses included data from 82 trials, four overviews and six regulatory reports and there were 1,968 major cardiovascular events identified for analysis. Patients randomly assigned to SGLT2 had lower risks of major cardiovascular events (RR 0.85, 95%CI 0.77–0.93), heart failure (RR 0.67, 95%CI 0.55–0.80), all-cause death (RR 0.79, 95%CI 0.70–0.88) and serious decline in kidney function (RR 0.59, 0.49–0.71). Significant adverse effects were observed for genital infections (RR 3.06, 95%CI 2.73–4.43), volume depletion events (RR 1.24, 95%CI 1.07–1.43) and amputation (RR 1.44 95%CI 1.13–1.83). There was a high likelihood of differences in the associations of the individual compounds with cardiovascular death, hypoglycaemia and amputation (all I2 > 80%) and a moderate likelihood of differences in the associations with non-fatal stroke, all-cause death, urinary tract infection and fracture (all I2 > 30%).
Conclusion
There are strong overall associations of SGLT2 inhibition with protection against major cardiovascular events, heart failure, serious decline in kidney function and all-cause death. SGLT2 inhibitors were also associated with infections, volume depletion effects and amputation. Some associations appear to differ between compounds.
Date Issued
2018-06-01
Date Acceptance
2018-03-16
Citation
Diabetes Research and Clinical Practice, 2018, 140, pp.118-128
ISSN
0168-8227
Publisher
Elsevier
Start Page
118
End Page
128
Journal / Book Title
Diabetes Research and Clinical Practice
Volume
140
Copyright Statement
© 2018 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000434107600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Diabetes type 2
SGLT2 inhibitors
Cardiovascular disease
Kidney disease
Safety
Amputation
Fracture
Systematic review
Randomised controlled trials
RANDOMIZED CONTROLLED-TRIAL
CHRONIC KIDNEY-DISEASE
ADD-ON THERAPY
DOUBLE-BLIND
BLOOD-PRESSURE
GLYCEMIC CONTROL
CLINICAL-TRIALS
INITIAL COMBINATION
JAPANESE PATIENTS
SGLT2 INHIBITORS
Publication Status
Published
Date Publish Online
2018-03-28