Efficacy and safety of novel antidiabetic drugs in patients with type 2 diabetes and chronic kidney disease: a network meta-analysis

Background: A number of novel antidiabetic drugs have been developed. These drugs include sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is). However, the optimal medication for individuals with type 2 diabetes mellitus (T2DM) and comorbid chronic kidney disease (CKD) has not been established. To this end, this study was conducted to compare specific novel antidiabetic drugs regarding efficacy and safety. Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications dated as of July 9, 2025. Cochrane risk of bias tool version 2.0 (RoB 2.0) was applied to measure the quality of the publications, and R 4.2.2 and Stata 15.1 were used to execute a Bayesian network meta-analysis (NMA). Primary outcomes encompassed major adverse cardiovascular events (MACEs), composite renal outcomes, and all-cause mortality (ACM). Secondary outcomes comprised adverse events (AEs), hypoglycemia, and cardiovascular death. Results: This NMA incorporated 30 studies, involving 39,844 participants with T2DM and comorbid CKD. The interventions were ranked by performance in various outcomes using the surface under the cumulative ranking curve (SUCRA) values. Sotagliflozin ranked first in reducing MACEs (SUCRA: 90.57%). Empagliflozin ranked first in improving composite renal outcomes (SUCRA: 89.76%) and reducing ACM (SUCRA: 72.38%). Canagliflozin ranked first in reducing AEs (SUCRA: 83.37%). Dapagliflozin + exenatide ranked first in reducing hypoglycemic events (SUCRA: 77.74%). Semaglutide ranked first in reducing cardiovascular mortality (SUCRA: 89.46%). Conclusion: Novel antidiabetic drugs offer benefits for patients with T2DM and comorbid CKD. However, the optimal intervention varies for different outcomes. Further clinical studies are anticipated to validate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251146144.