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

Rev Cardiovasc Med. 2021 Dec 22;22(4):1479-1490. doi: 10.31083/j.rcm2204152.

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: Cardiorenal syndrome; Cardiovascular outcomes; Chronic kidney disease; Heart failure; Mortality; Myocardial infarction; Randomized controlled trials.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2*
  • Glucose
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Renal Insufficiency, Chronic* / diagnosis
  • Renal Insufficiency, Chronic* / drug therapy
  • Renal Insufficiency, Chronic* / epidemiology
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects

Substances

  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucose