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.