In the largest network meta-analysis comparing three drug classes for diabetic kidney disease, SGLT-2 inhibitors led for blood sugar and weight reduction, GLP-1 agonists (liraglutide) were best at lowering cholesterol, and semaglutide was gentlest on kidney filtration rate.
99,599 patients across 39 trialsLargest network meta-analysis comparing SGLT-2 inhibitors, GLP-1 agonists, and finerenone for diabetic kidney disease
What the researchers found
Across 39 RCTs and 99,599 patients, each drug class showed distinct advantages:
**SGLT-2 inhibitors** were superior for HbA1c reduction (MD -0.33), blood pressure lowering (systolic MD -5.52 to -1.50), and weight loss (MD -3.81 to -1.29 kg). Empagliflozin ranked highest for HbA1c and diastolic blood pressure reduction. Canagliflozin ranked best for systolic blood pressure and weight loss.
**GLP-1 receptor agonists**: Liraglutide was the most effective agent for LDL cholesterol reduction (MD -1.58 to -1.41). Semaglutide was the least harmful to estimated GFR, an important consideration in kidney disease patients.
**Finerenone** significantly reduced systolic blood pressure (MD -1.65) and had the lowest urinary tract infection rate.
Safety profiles were generally favorable across all classes, with different drugs showing advantages for specific adverse events.
Why it matters
Diabetic kidney disease is one of the leading causes of kidney failure worldwide, and clinicians now have three powerful drug classes to choose from — but until this analysis, there was no comprehensive head-to-head comparison across all three. This network meta-analysis helps answer a critical clinical question: for a specific patient with diabetic kidney disease, which drug class offers the best combination of benefits and lowest risk?
How the study worked
This was a systematic review and network meta-analysis following PRISMA-NMA guidelines, registered on PROSPERO. Researchers searched seven databases through November 2023 for randomized controlled trials comparing SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone in type 2 diabetes patients with non-dialysis chronic kidney disease. They assessed bias using RoB 2.0, evidence confidence using CINeMA, and performed traditional and network meta-analyses with random-effects models. Surface under the cumulative ranking curve (SUCRA) scores ranked treatments.
What this study cannot tell us
Network meta-analysis relies on indirect comparisons across trials with different designs, populations, and follow-up periods. The included studies varied in CKD stage, baseline characteristics, and drug dosing. Some specific drug comparisons had limited evidence. The analysis focused on surrogate outcomes (HbA1c, blood pressure, weight) rather than hard endpoints like kidney failure or death. Publication bias may affect results. The search was limited to November 2023, missing more recent trial data.
How to read the evidence
This is a network meta-analysis of 39 randomized controlled trials — a high level of evidence for comparative effectiveness. However, network meta-analyses rely partly on indirect comparisons and may be affected by heterogeneity between included studies.
When this study was published
Published in 2025 with data through November 2023, this is a current and clinically relevant analysis. The field is evolving rapidly with new trial results for these drug classes.
The bigger picture
This analysis arrives at a pivotal moment in diabetic kidney disease management. All three drug classes have demonstrated kidney-protective effects in landmark trials (CREDENCE, DAPA-CKD for SGLT-2i; FLOW for semaglutide; FIDELIO/FIGARO for finerenone), and guidelines now recommend layering these drugs. This network meta-analysis helps distinguish their relative strengths, supporting a personalized approach where drug selection is tailored to each patient's primary risk factors — whether that's hyperglycemia, obesity, cholesterol, or kidney function decline.
Questions still open
- Is combining SGLT-2 inhibitors with GLP-1 agonists more effective than either alone for slowing diabetic kidney disease progression?
- Do the relative advantages of each drug class change depending on the stage of chronic kidney disease?
- How does tirzepatide compare to these agents for diabetic kidney disease, given its dual GLP-1/GIP mechanism?
Common questions
Which drug class is best for someone with diabetic kidney disease?
Are these drugs safe for people with kidney disease?
Read the original research
Clinical efficacy and safety of sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor, glucagon-like peptide-1 (GLP-1) receptor agonist, and Finerenone in type 2 diabetes mellitus with non-dialysis chronic kidney disease: a network meta-analysis of randomized clinical trials.
Frontiers in pharmacology, 16, 1517272
Citation
Guo, Jingyi; Wei, Maoying; Zhang, Wenhua; Jiang, Yijia; Li, Aijing; Wang, Churan; Yin, Dan; Sun, Anning; Gong, Yanbing. (2025). Clinical efficacy and safety of sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor, glucagon-like peptide-1 (GLP-1) receptor agonist, and Finerenone in type 2 diabetes mellitus with non-dialysis chronic kidney disease: a network meta-analysis of randomized clinical trials.. Frontiers in pharmacology, 16, 1517272. https://doi.org/10.3389/fphar.2025.1517272