AIMS: Type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) is a common complication that increases the risk of cardiovascular (CV) events and kidney failure. Recent therapies, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase IV (DPP-4) inhibitors, show promise in improving outcomes. However, evidence of their comparative effectiveness in reducing CV and renal outcomes is scarce.
MATERIALS AND METHODS: We searched electronic databases such as PubMed, Scopus, and clinical trial registries for randomized controlled trials (RCTs) published between 2014 and 2024. A network meta-analysis (NMA) was employed to evaluate the effectiveness of antidiabetic drugs on cardiorenal outcomes. Primary outcomes were (1) major adverse CV events (MACE), (2) composite renal outcomes, (3) all-cause mortality. Other outcomes included heart failure (HF), stroke, macroalbuminuria, and a decline in estimated glomerular filtration rate (eGFR) >40% or renal replacement therapy.
RESULTS: Twenty-six studies with 143 296 participants with T2DM and CKD were included. SGLT2 inhibitors were highly effective in reducing the risk of renal outcomes such as composite events (P-score: 0.94), eGFR decline >40% or renal replacement therapy (0.99) and CV outcomes such as MACE (0.93) and HF (1.00) followed by GLP-1 RA. While GLP-1 RA was particularly effective in reducing the risk of MI (0.87), macroalbuminuria (0.86) and stroke (0.83) compared to SGLT2 inhibitors. Both SGLT2 inhibitors and GLP-1 receptor agonists are highly effective (0.83) in reducing all-cause mortality. DPP-4 inhibitors had limited benefits compared to SGLT2 inhibitors and GLP-1 RA.
CONCLUSION: SGLT2 inhibitors followed by GLP-1 RA provide strong benefits for CV and kidney health in patients with T2DM and CKD. SGLT2 inhibitors demonstrate superior benefit over GLP-1 receptor agonists for HF and renal outcomes, highlighting their preferred role in these clinical scenarios.
