Cardiovascular outcomes of glucose lowering therapy in chronic kidney disease patients: a systematic review with meta-analysis

Kamdar, A. , Sykes, R. , Morrow, A. , Mangion, K. and Berry, C. (2021) Cardiovascular outcomes of glucose lowering therapy in chronic kidney disease patients: a systematic review with meta-analysis. Reviews in Cardiovascular Medicine, 22(4), pp. 1479-1490. (doi: 10.31083/j.rcm2204152) (PMID:34957787)

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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.

Item Type:Articles
Additional Information:Professor Colin Berry is supported by research funding from the British Heart Foundation (PG/17/25/32884; RE/13/5/30177; RE/18/6/34217). Dr Andrew Morrow is supported by research funding from the Medical Research Council (MR/S018905/1). Dr Kenneth Mangion is supported by research funding from the Chief Scientist Office (COV/LTE/20/10, COV/GLA/20/05)
Glasgow Author(s) Enlighten ID:Berry, Professor Colin and Kamdar, Anna and Mangion, Dr Kenneth and Sykes, Dr Robert and Morrow, Dr Andrew
Authors: Kamdar, A., Sykes, R., Morrow, A., Mangion, K., and Berry, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Reviews in Cardiovascular Medicine
Publisher:IMR Press
ISSN (Online):2153-8174
Published Online:21 December 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Reviews in Cardiovascular Medicine 22(4): 1479-1490
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
301454CORonary MICrovascular Angina (CorMicA): a pilot trial with a nested MRI sub-studyColin BerryBritish Heart Foundation (BHF)PG/17/25/32884CAMS - Cardiovascular Science
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
303684A randomized, double-blind, placebo-controlled Phase 2A cross-over trial of oral zibotentan in patients with angina due to small vessel disease: a proof-of-concept, developmental trial for safety, efficacy and biomarkers developmentColin BerryMedical Research Council (MRC)MR/S018905/1CAMS - Cardiovascular Science
313234COVID-19 long term effects; a randomised clinical trial of resistance exercise and trial platformColin BerryOffice of the Chief Scientific Adviser (CSO)COV/LTE/20/10CAMS - Cardiovascular Science