Network meta-analysis of novel antidiabetic drugs in T2DM with CKD shows sotagliflozin, empagliflozin, and semaglutide rank highest for cardiovascular and renal outcomes.
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Key Takeaway
Consider that novel antidiabetic drugs vary in efficacy for specific outcomes in T2DM with CKD; further studies are needed to validate findings.
This network meta-analysis assessed the efficacy and safety of novel antidiabetic drugs in patients with type 2 diabetes mellitus and comorbid chronic kidney disease. The analysis included 39,844 participants and compared sotagliflozin, empagliflozin, canagliflozin, dapagliflozin, exenatide, and semaglutide against other agents. Primary outcomes included major adverse cardiovascular events (MACEs), composite renal outcomes, and all-cause mortality, while secondary outcomes covered adverse events, hypoglycemia, and cardiovascular death.
Sotagliflozin ranked first for reducing MACEs with a SUCRA of 90.57%. Empagliflozin ranked first for improving composite renal outcomes (SUCRA: 89.76%) and reducing all-cause mortality (SUCRA: 72.38%). Semaglutide ranked first for reducing cardiovascular mortality (SUCRA: 89.46%). Regarding safety, canagliflozin ranked first in reducing adverse events (SUCRA: 83.37%), while the combination of dapagliflozin and exenatide ranked first for reducing hypoglycemic events (SUCRA: 77.74%).
The study notes that further clinical studies are anticipated to validate these findings. While novel antidiabetic drugs offer benefits for patients with T2DM and comorbid CKD, the optimal intervention varies depending on the specific clinical outcome of interest. Absolute numbers and p-values were not reported in the source data. Clinicians should interpret these rankings as probabilistic preferences rather than absolute efficacy differences until head-to-head trials confirm these associations.
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View Original Abstract ↓
BackgroundA 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.MethodsPubMed, 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.ResultsThis 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%).ConclusionNovel 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 Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251146144.
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