How Dulaglutide Protects Kidneys: It Lowers 14 Proteins Linked to Kidney Failure | Research

The takeaway

Dulaglutide reduced plasma levels of 14 proteins linked to kidney failure progression, especially TNF receptors driving inflammation, in diabetic patients with CKD.

14 of 21 proteins
Dulaglutide significantly lowered 14 out of 21 proteins that predict progression to end-stage kidney disease, while these proteins worsened on insulin

What the researchers found

In patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD), 6 months of dulaglutide treatment significantly lowered plasma levels of 14 out of 21 proteins previously linked to progression to end-stage kidney disease. The most dramatically affected were 8 TNF receptor family proteins (TNF-R1, -R2, -R3, -R4, -R6B, -R7, -R19L, -R27) — key drivers of inflammation and cell death pathways.

In contrast, these same proteins increased in patients on insulin glargine. The differences were most pronounced in patients with worse baseline kidney function, higher albumin leakage, higher HbA1c, or higher BMI — suggesting dulaglutide's kidney-protective effects may be strongest in the sickest patients. Kidney injury molecule 1 (KIM1), a marker of tubular damage, declined in both groups equally.

Why it matters

CKD progresses to kidney failure in millions of people, and diabetic kidney disease is the leading cause. While the AWARD-7 trial showed dulaglutide slowed kidney decline, nobody knew why at the molecular level. This study reveals that dulaglutide suppresses a broad panel of inflammatory and fibrotic proteins — particularly TNF receptors — that drive kidney damage. This provides concrete biological evidence for how GLP-1 drugs protect kidneys, beyond just improving blood sugar and weight.

The numbers in context

n=249 (124 dulaglutide, 125 insulin glargine) · 6 months · 14 of 21 kidney proteins improved · 8 TNF receptors most affected · effects strongest in worse baseline CKD · 21-protein Joslin Kidney Panel

How the study worked

Post hoc proteomic analysis of the AWARD-7 RCT. Plasma from 249 participants with T2D and CKD was analyzed using a customized OLINK proteomic platform measuring 21 proteins from the Joslin Kidney Panel (JKP), previously validated as predictors of end-stage kidney disease. Changes from baseline to 6 months were compared between dulaglutide and insulin glargine groups.

Who was studied

249 adults with type 2 diabetes and moderate-to-severe CKD from the AWARD-7 trial (124 dulaglutide, 125 insulin glargine)

What this study cannot tell us

Post hoc analysis — the trial was not designed to test proteomic endpoints. The Joslin Kidney Panel proteins are biomarkers of risk, so lowering them doesn't prove kidney damage was prevented (association vs. causation). The 6-month timeframe is relatively short for kidney disease progression. Proteomic changes may reflect systemic metabolic improvements rather than direct kidney effects. Sample size of 249 is moderate for proteomic analyses. The insulin glargine comparator doesn't represent untreated patients.

How to read the evidence

This is a post hoc analysis of a randomized controlled trial using a validated proteomic kidney panel. The 'Moderate' grade reflects the strong parent trial design but acknowledges the post hoc nature of the analysis and the biomarker-based (rather than clinical endpoint) outcomes.

When this study was published

Published in 2026, this is the most recent study in the growing evidence base for GLP-1 renoprotection. It builds on the AWARD-7 trial data with state-of-the-art proteomics to explain the molecular mechanisms.

The bigger picture

GLP-1 drugs are increasingly recognized for protecting organs beyond the pancreas — the heart, brain, and kidneys. This proteomic study provides one of the most detailed molecular explanations for how a GLP-1 drug protects the kidneys. The finding that TNF receptor family proteins are the primary targets aligns with growing evidence that inflammation is a key driver of diabetic kidney disease progression, and suggests GLP-1 drugs may work partly as anti-inflammatory agents in the kidney.

Questions still open

Do all GLP-1 receptor agonists (semaglutide, liraglutide) produce the same TNF receptor suppression in CKD patients?
Could these proteomic biomarkers be used to monitor kidney protection in real-time during GLP-1 therapy?
Is the kidney protection from dulaglutide primarily an anti-inflammatory effect or does it work through other mechanisms too?

Common questions

What are TNF receptors and why do they matter for kidney disease?

TNF (tumor necrosis factor) receptors are proteins involved in inflammation and programmed cell death. When their levels are elevated in the blood, it signals that inflammatory and destructive processes are actively damaging the kidneys. The fact that dulaglutide significantly lowered 8 different TNF receptors suggests it may protect kidneys by broadly suppressing the inflammatory cascade that drives chronic kidney disease progression.

Does this mean dulaglutide can prevent kidney failure?

This study shows dulaglutide lowers biomarkers associated with kidney failure progression, which is encouraging but not the same as proving it prevents kidney failure. The parent AWARD-7 trial did show dulaglutide slowed kidney function decline compared to insulin. This proteomic data helps explain how that protection may work. Whether it can prevent end-stage kidney disease would need to be confirmed in longer trials with clinical endpoints.

Read the original research

Dulaglutide Effect on Proteins Associated With CKD Progression.

Kidney international reports, 11(4), 103789

View on PubMed ↗Publisher’s paper ↗

Citation

McFarlin, Brandon E; Tye, Sok Cin; Satake, Eiichiro; Md Dom, Zaipul I; Kechter, Afton; Wilson, Jonathan M; Krolewski, Andrzej S; Duffin, Kevin L. (2026). Dulaglutide Effect on Proteins Associated With CKD Progression.. Kidney international reports, 11(4), 103789. https://doi.org/10.1016/j.ekir.2026.103789