The Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists on Cardiorenal Outcomes: Systematic Review and Meta-analysis

BACKGROUND: Evidence for the cardiorenal risk reduction properties of antihyperglycemic medications originally prescribed for type 2 diabetes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) is rapidly emerging. We completed a meta-analysis of recent literature to provide evidence-based estimates of benefit across various populations and outcomes. METHODS: We searched Medline and Cochrane databases from 2015 to September 2021 for randomized controlled trials of SGLT2i and GLP-1RA with placebo control. Reviewers screened citations, extracted data, and assessed the risk of bias and certainty of evidence. We assessed statistical and methodological heterogeneity and performed a meta-analysis of studies with similar interventions and components. RESULTS: A total of 137,621 adults (51% male) from 19 studies were included; 14 studies with unclear risk of bias and 5 with low risk of bias. Compared with standard of care, use of SGLT2i showed significant reductions for the outcome of cardiovascular (CV) mortality (14%), any-cause mortality (13%), major adverse CV events (MACE) (12%), heart failure (HF) hospitalization (31%), CV death or HF hospitalization (24%), nonfatal myocardial infarction (10%), and kidney composite outcome (36%). Treatment with GLP-1RA was associated with significant reductions for the outcome of CV mortality (13%), any-cause mortality (12%), MACE (14%), CV death or HF hospitalization (11%), nonfatal stroke (16%), and kidney composite outcome (22%). CONCLUSIONS: The use of GLP-1RA and SGLT2i leads to a statistically significant benefit across most cardiorenal outcomes in the populations studied. This review shows a role for SGLT2i and GLP-1RA in cardiorenal protection in adults, independent of type 2 diabetes status.