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

Zhu X, Wang X, Zhang P, Yang Z, Zhao N, Li J, Shi Y, Zhao Y, Ma J

Frontiers in endocrinology31 Mar 2026

PMID41987895PMCIDPMC13076170DOI10.3389/fendo.2026.1750615PepBankPUB-41987895

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

1 result from studies that gave the peptide. 1 result from people.

01HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and chronic kidney disease, semaglutide ranked first for reducing cardiovascular mortality among the novel antidiabetic drugs in a network meta-analysis.
In plain wordsIn adults with type 2 diabetes and kidney disease, semaglutide ranked first among the compared drugs for lowering death from heart and vessel causes.
Peptide
Semaglutide
Outcome
DecreaseCardiovascular mortality ranking (SUCRA)
Study
n: not reported in source
Analysis
Secondary
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Measurements
SUCRA
89.46%
cardiovascular mortality
Source sentences
Summary
Semaglutide ranked first in reducing cardiovascular mortality (SUCRA: 89.46%).
1 context sentence(design, population, supporting numbers)
Summary · context
This NMA incorporated 30 studies, involving 39,844 participants with T2DM and comorbid CKD.
Show in the study text Report a problemFND-4198789501

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Version history

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Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

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