Treatment of Diabetic Kidney Disease. A Network Meta-analysis

Fabian Büttner , Clara Vollmer Barbosa, Hannah Lang, Zhejia Tian, Anette Melk , Bernhard M. W. Schmidt


Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.


Diabetes mellitus (DM) ranks among the top ten most devastating diseases worldwide, contributing to enormous disability and mortality [1]. The major burden of DM is primarily driven by its complications, among which diabetic kidney disease (DKD) is one of the most harmful. The incidence of DKD has globally substantially increased over the past three decades [2], which lead to the inevitable necessity to develop novel effective drugs to preserve kidney function, decrease the cardiovascular risk or even prevent its onset.

The treatment of DKD is based on renin-angiotensin-aldosterone system (RAAS) blockade since the 90´s. RAAS is a hormonal system that regulates the fluid and electrolyte balance and the systemic vascular system in the human body through various pathways, that affect the kidney.


The protocol for this analysis was registered with Prospero (CRD42021238011) and reported according to the PRISMA statements 2020 (S3 File).

We searched Cochrane Central Register of Controlled Trials (CENTRAL), Medline and by the following search terms: (diabetic nephropathy OR (diabetes AND kidney) OR chronic kidney disease OR CKD) AND (RCT OR randomized) combined with names of the investigated drugs (S4 File). We included only prospective, randomized, controlled clinical trials published in English from 1995 till May 2022 on with a minimum duration of 8 weeks. The deliberate choice of 8 weeks minimum allowed the inclusion of studies with specific safety endpoints (e.g., hyperkalemia). We excluded cross-over trials and retracted publications. Control groups met our inclusion criteria if they consisted of an intervention included in our analysis or a placebo on the background treatment with single ACEi/ARB


Our literature search initially yielded 3489 publications, out of which 38 clinical trials were found fully eligible, in total including 42346 patients.


This network meta-analysis comprises data from 42346 patients with DKD. This high number allows a comprehensive analysis on the comparative effectiveness of various drug regimens. On top of treatment with ACEi or ARB only SGLT2 inhibition caused a decrease in mortality and in the incidence of ESKD. Therefore, SGLT2i should be an essential part of the treatment of each patient with DKD in addition to ACEi or ARB. We for the first time compared all interventions meant to reduce progression of DKD and have been used from nephrologists during the last two decades.

Citation: Büttner F, Barbosa CV, Lang H, Tian Z, Melk A, Schmidt BMW (2023) Treatment of diabetic kidney disease. A network meta-analysis. PLoS ONE 18(11): e0293183.

Editor: Licy Yanes Cardozo, University of Mississippi Medical Center, UNITED STATES

Received: January 29, 2023; Accepted: October 7, 2023; Published: November 2, 2023

Copyright: © 2023 Büttner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting information files.

Funding: BMWS received honoraria for lectures/consulting from AstraZeneca and Bayer Vital. These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.