DPP-4 Inhibitor Protects Kidneys From Cyclosporine Toxicity Through GLP-1 Pathway | Research

The takeaway

The DPP-4 inhibitor omarigliptin combined with shikonin protected against cyclosporine-induced kidney damage by preserving GLP-1 signaling and reducing inflammation and oxidative stress.

GLP-1 protects kidneys
DPP-4 inhibitor-preserved GLP-1 signaling reduced cyclosporine kidney damage through anti-inflammatory and antioxidant mechanisms

What the researchers found

Omarigliptin/shikonin combination protected against cyclosporine nephrotoxicity by preserving GLP-1 signaling, reducing inflammation, and mitigating oxidative stress in kidney tissue.

Why it matters

Cyclosporine kidney damage limits its long-term use in transplant patients. If DPP-4 inhibitors can protect kidneys through GLP-1 preservation, transplant patients could use cyclosporine more safely for longer.

The numbers in context

Specific dose levels and kidney function measurements were analyzed but not detailed in the available abstract.

How the study worked

Animal study testing omarigliptin (DPP-4 inhibitor) and shikonin combination in cyclosporine-induced nephrotoxicity model. Assessed kidney function, GLP-1 levels, inflammatory markers, and oxidative stress.

Who was studied

Rats in a cyclosporine-induced nephrotoxicity model

What this study cannot tell us

Animal study. Combination therapy adds complexity. The specific contributions of omarigliptin vs shikonin need dissection. Human translation requires clinical trials in transplant patients.

How to read the evidence

Preliminary evidence: animal study demonstrating kidney protection through GLP-1 pathway preservation during immunosuppressive therapy.

When this study was published

Published in 2025. Expands GLP-1 kidney protection evidence to drug-induced nephrotoxicity.

The bigger picture

The GLP-1/DPP-4 axis is revealing kidney-protective properties across many contexts — from diabetic nephropathy to drug-induced toxicity. This expanding evidence suggests GLP-1-based therapies could become standard kidney-protective agents in various clinical settings.

Questions still open

Should transplant patients on cyclosporine receive DPP-4 inhibitors for kidney protection?
Does GLP-1 preservation provide kidney protection beyond what its glucose-lowering effects explain?
Could GLP-1 receptor agonists provide even stronger kidney protection than DPP-4 inhibitors in this setting?

Common questions

How does a DPP-4 inhibitor protect kidneys?

DPP-4 inhibitors prevent the breakdown of GLP-1, a peptide hormone with anti-inflammatory and protective properties. By maintaining higher GLP-1 levels, the kidneys are better protected from the toxic effects of cyclosporine.

Could this help transplant patients?

Potentially. Cyclosporine kidney damage is a major problem in transplant medicine. If DPP-4 inhibitors can protect kidneys while patients take cyclosporine, it could allow longer and safer use of this essential anti-rejection drug.

Read the original research

Omarigliptin/shikonin combination alleviates cyclosporine-induced nephrotoxicity: The role of sirtuin 1, glucagon-like peptide-1, HMGB1/RAGE/TLR4 signaling, and p38/ERK/JNK MAPKs.

Human & experimental toxicology, 44, 9603271251394693

View on PubMed ↗Publisher’s paper ↗

Citation

Abdallah, Marwa H; Atia, Hanan Abdelmawgoud; Elariny, Hemat A; Khalifa, Amany M; Saleh, Asmaa; Kabel, Ahmed M. (2025). Omarigliptin/shikonin combination alleviates cyclosporine-induced nephrotoxicity: The role of sirtuin 1, glucagon-like peptide-1, HMGB1/RAGE/TLR4 signaling, and p38/ERK/JNK MAPKs.. Human & experimental toxicology, 44, 9603271251394693. https://doi.org/10.1177/09603271251394693