IMR Press / RCM / Volume 22 / Issue 4 / DOI: 10.31083/j.rcm2204152
Open Access Systematic Review
Cardiovascular outcomes of glucose lowering therapy in chronic kidney disease patients: a systematic review with meta-analysis
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1 Institute of Cardiovascular and Medical Sciences, University of Glasgow, G12 8TA Glasgow, UK
2 West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, G81 4DY Glasgow, UK
3 Department of Cardiology, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde Health Board, G51 4TF Glasgow, UK
*Correspondence: robert.sykes@glasgow.ac.uk (Robert Sykes)
Academic Editor: Grigorios Korosoglou
Rev. Cardiovasc. Med. 2021, 22(4), 1479–1490; https://doi.org/10.31083/j.rcm2204152
Submitted: 5 September 2021 | Revised: 13 October 2021 | Accepted: 19 October 2021 | Published: 22 December 2021
(This article belongs to the Special Issue State-of-the-Art Cardiovascular Medicine in Europe 2022)
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

Chronic kidney disease (CKD) and cardiovascular disease share common risk factors such as hypertension, diabetes mellitus and dyslipidemia. Patients with CKD carry a high burden of cardiovascular disease and may be excluded from clinical trials on the basis of safety. There are an increasing number of clinical trials which predefine sub-group analysis for CKD. This systematic review with fixed-effect meta-analysis investigates glucose lowering therapy and cardiovascular outcomes in relation to CKD. We included randomized controlled trials (RCT) of glucose lowering treatments performed in adults (aged 18 years), humans, with no restriction on date, and English-language restriction in patients with pre-existing CKD regardless of diabetes status. Embase & Ovid Medline databases were searched up to April 2021. Risk of bias was assessed according to Revised Cochrane risk-of-bias tool. We included 7 trials involving a total of 48,801 participants. There were 4 sodium-glucose cotransporter-2 inhibitors (SGLT2i), 2 glucagon-like peptide-1 receptor (GLP-1R) agonists and 1 Dipeptidyl-peptidase 4 (DPP4) inhibitor identified. SGLT2i (relative risk (RR) = 0.90, 95% confidence interval (CI) [0.79–1.02]) and GLP-1R agonists (RR = 0.83, 95% CI [0.72–0.96]) were associated with a reduction in cardiovascular death. SGLT2i (RR = 0.69, 95% CI [0.63–0.75]) are also associated with a reduction in hospitalization for heart failure. In summary, this meta-analysis of large, RCTs of glucose lowering therapies has demonstrated that treatment with SGLT2i or GLP-1R agonists may improve 3 point-MACE and cardiovascular outcomes in patients with chronic renal failure compared with placebo. This systematic review was registered with the PROSPERO network (registration number: CRD42021268563) and follows the PRISMA guidelines on systematic reviews and metanalysis.

Keywords
Cardiovascular outcomes
Randomized controlled trials
Chronic kidney disease
Mortality
Myocardial infarction
Heart failure
Cardiorenal syndrome
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