Abstract
Aims
Both sodium-glucose cotransporter-2 (SGLT-2) inhibitors and mineralocorticoid receptor
antagonists (MRAs) have been shown to reduce cardiovascular (CV) event in patients
with type 2 diabetes (T2D) and chronic kidney disease (CKD). However, little evidence
pertains to the benefits of their combined use.
Methods
We systematically searched the PubMed, MEDLINE, EMBASE, and Cochrane Library databases
through July 2022. We selected randomized controlled trials comparing SGLT-2 inhibitors,
MRAs, or SGLT-2 inhibitor + MRA combination therapy, with placebo in patients with
T2D and CKD. We performed a network meta-analysis to indirectly compare the treatments. The primary outcome was a composite
of CV events.
Results
Eight studies were selected with 36,186 patients. The primary outcome was significantly
improved in the combination therapy group compared with the other groups (RR [95%
CI]; vs SGLT-2 inhibitors, 0.76 [0.60; 0.96]; vs MRAs, 0.66 [0.53; 0.82]; vs placebo,
0.58 [0.47; 0.73]). Additionally, the combination therapy was associated with a considerable
reduction in the risk of hyperkalemia (RR vs MRA, 0.43 [0.23; 0.79]).
Conclusion
Combination of SGLT-2 inhibitors and MRAs potentially reduced CV events compared with
SGLT-2 inhibitors or MRAs alone. This combination may be a candidate treatment strategy
for patients with T2D and CKD.
Keywords
Abbreviations:
T2D (type 2 diabetes), CKD (chronic kidney disease), ESKD (end-stage kidney disease), CV (cardiovascular), RAS (renin-angiotensin system), SGLT-2 (sodium-glucose cotransporter-2), MRA (mineralocorticoid receptor antagonist), PRISM (Preferred Reporting Items for Systematic Reviews and meta-Analyses), PROSPERO (International Prospective Register of Systematic Reviews), eGFR (estimated glomerular filtration rate), UACR (urinary albumin/creatinine ratio), Cr (creatinine), RCT (randomized controlled trial), MI (myocardial infarction), HF (heart failure), AE (adverse event), RR (risk ratio), CI (confidence interval)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: November 16, 2022
Accepted:
November 14,
2022
Received in revised form:
October 25,
2022
Received:
September 22,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
