Comparative analysis on renal and cardiovascular outcomes of antidiabetic treatment in chronic kidney disease patients—A systematic review and network meta‐analysis

Abstract 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.