Evaluation of the protective effects of liraglutide, dapagliflozin and their combination in rat kidneys of streptozotocin induced diabetes

Liraglutide, but not dapagliflozin, reduced renal inflammation and fibrosis in a rat model of streptozotocin-induced diabetes. Combined treatment produced the strongest glucose reduction but did not improve renal inflammation or fibrosis beyond liraglutide alone.

Observational study — controlled animal study. Population: adult Wistar rats with streptozotocin-induced diabetes. Sample size: 15-17 rats per group. Follow-up: 8 weeks. Interventions: dapagliflozin 1 mg/kg orally; liraglutide 0.4 mg/kg subcutaneously; combination of dapagliflozin and liraglutide.

Both dapagliflozin and liraglutide lowered glucose, and the combined group showed the strongest reduction. Diabetes increased kidney-to-body weight ratio, but this was unchanged by treatment. Diabetes raised renal CRP, TNF-α, IL-6, and TBARS but not endothelin-1, MCP-1, or GPx. Liraglutide normalized CRP and TNF-α, whereas dapagliflozin did not. Liraglutide also normalized renal fibrosis, TGF-β, and collagen type IV, while dapagliflozin did not; all treatments reduced nitric oxide.

Researchers studying liraglutide in diabetic kidney disease would care because this paper offers preclinical evidence that liraglutide attenuates renal inflammation and fibrosis in STZ-induced diabetes, whereas dapagliflozin did not. It does not establish efficacy or dosing in humans, nor whether combination therapy improves renal outcomes over liraglutide alone.

Key findings

• Dapagliflozin and liraglutide each reduced glucose levels, with the strongest reduction in the combined group.
• Diabetes increased kidney-to-body weight ratio, and none of the treatments altered this ratio.
• Diabetes increased renal CRP, TNF-α, IL-6, and TBARS but did not change endothelin-1, MCP-1, or GPx.
• Liraglutide normalized CRP and TNF-α, and adding dapagliflozin provided no additional improvement.
• All three treatments reduced nitric oxide, but none changed IL-6, TBARS, or GPx levels.
• Liraglutide, but not dapagliflozin, normalized renal fibrosis, TGF-β, and collagen type IV.

Limitations

• Findings from a rat model may not translate to humans.
• Treatment duration was only 8 weeks.
• Randomization, blinding, and sample size calculations were not described.

The record

• Journal: Journal of diabetes and its complications 40(8): 109362
• Published: 2026-06-21
• PMID: 42341385 — DOI: 10.1016/j.jdiacomp.2026.109362
• MeSH terms: Kidney, Animals, Rats, Rats, Wistar, Diabetic Nephropathies, Diabetes Mellitus, Experimental, Fibrosis, Benzhydryl Compounds, Streptozocin, Glucosides, Blood Glucose, Hypoglycemic Agents, Drug Therapy, Combination, Oxidative Stress, Male, Liraglutide
• Funding: Jordan University of Science and Technology Deanship of Research; Jordan University of Science and Technology
• Author countries: Jordan

Peptide profiles: Liraglutide.

All indexed evidence: Liraglutide trials & papers.

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