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Study · Animal study (in vivo) · mouse · 2026

9 results

Comparative effects of semaglutide tirzepatide and retatrutide on renal fibrosis in UUO and aged mice.

Ding M, Li X, Wei Y, Wang J, Jiao B, Li C, Ma W, Peng Y, Shen J, Yu G, Gao C

iScience13 Aug 2026

PMID42630988 (opens in a new tab)PMCIDPMC13495082 (opens in a new tab)DOI10.1016/j.isci.2026.117174 (opens in a new tab)PepBankPUB-42630988
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Summary

Chronic kidney disease is a major health burden. Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models. Integrating in vivo and in vitro data showed model- and drug-specific patterns of action among the three agents. In the UUO model, semaglutide effects were associated with PI3K-AKT inhibition, tirzepatide effects with PI3K-AKT inhibition and PPAR pathway activation, and retatrutide effects with concurrent inhibition of both PI3K-AKT and NF-κB pathways. In the aging model, all three drugs were linked to G2/M arrest mitigation. Retatrutide showed the greatest efficacy at the doses tested in the models studied. This comparative study offers a framework for understanding the renoprotective actions of these drugs and generates hypotheses for future investigation.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    In mice with unilateral ureteral obstruction (UUO), retatrutide effects were associated with inhibition of the PI3K-AKT pathway.

    In plain wordsIn mice with kidney scarring, retatrutide effects were linked to lower activity of the PI3K-AKT pathway.

    Peptide
    Retatrutide
    Outcome
    DecreasePI3K-AKT pathway activity in UUO model
    Study

    mousen: not reported in source

    UUO (unilateral ureteral obstruction) model
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    retatrutide effects with concurrent inhibition of both PI3K-AKT and NF-κB pathways.
    1 context sentence
    Summary · context
    Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In mice with unilateral ureteral obstruction (UUO), retatrutide effects were associated with concurrent inhibition of the NF-κB pathway.

    In plain wordsIn mice with kidney scarring, retatrutide effects were linked to lower activity of the NF-κB pathway.

    Peptide
    Retatrutide
    Outcome
    DecreaseNF-κB pathway activity in UUO model
    Study

    mousen: not reported in source

    UUO (unilateral ureteral obstruction) model
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    retatrutide effects with concurrent inhibition of both PI3K-AKT and NF-κB pathways.
    1 context sentence
    Summary · context
    Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In aged mice, retatrutide, like semaglutide and tirzepatide, was linked to mitigation of G2/M cell-cycle arrest.

    In plain wordsIn aged mice, retatrutide was linked to less G2/M cell-cycle arrest, as were semaglutide and tirzepatide.

    Peptide
    Retatrutide
    Outcome
    DecreaseG2/M cell-cycle arrest in aging model
    Study

    mousen: not reported in source

    Aging mouse model
    Outcome group
    Aging markers · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In the aging model, all three drugs were linked to G2/M arrest mitigation.
    1 context sentence
    Summary · context
    Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In the mouse and cell models studied, retatrutide showed the greatest efficacy of the three agents at the doses tested.

    In plain wordsIn mice and kidney cells, retatrutide worked best of the three drugs tested at the doses used.

    Peptide
    Retatrutide
    Outcome
    Not applicableAnti-fibrotic efficacy compared with semaglutide and tirzepatide
    Study

    mousen: not reported in source

    UUO and aging mouse models; HK-2 cells
    Comparator
    Semaglutide; tirzepatide
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Retatrutide showed the greatest efficacy at the doses tested in the models studied.
    1 context sentence
    Summary · context
    Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In mice with unilateral ureteral obstruction, semaglutide effects were associated with inhibition of the PI3K-AKT pathway.

    In plain wordsIn mice with kidney injury, semaglutide's effects were linked to lower PI3K-AKT pathway activity.

    Peptide
    Semaglutide
    Outcome
    DecreasePI3K-AKT pathway activity in UUO kidney
    Study

    mousen: not reported in source

    Mouse unilateral ureteral obstruction (UUO) model
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    semaglutide effects were associated with PI3K-AKT inhibition
    1 context sentence
    Summary · context
    Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In mice with unilateral ureteral obstruction, tirzepatide effects were associated with inhibition of the PI3K-AKT pathway.

    In plain wordsIn mice with kidney injury, tirzepatide's effects were linked to lower PI3K-AKT pathway activity.

    Peptide
    Tirzepatide
    Outcome
    DecreasePI3K-AKT pathway activity in UUO kidney
    Study

    mousen: not reported in source

    Mouse unilateral ureteral obstruction (UUO) model
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    tirzepatide effects with PI3K-AKT inhibition and PPAR pathway activation
    1 context sentence
    Summary · context
    Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.
  7. 07AnimalAnimal study (in vivo)Mechanism

    In mice with unilateral ureteral obstruction, tirzepatide effects were associated with activation of the PPAR pathway.

    In plain wordsIn mice with kidney injury, tirzepatide's effects were linked to higher PPAR pathway activity.

    Peptide
    Tirzepatide
    Outcome
    IncreasePPAR pathway activity in UUO kidney
    Study

    mousen: not reported in source

    Mouse unilateral ureteral obstruction (UUO) model
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    tirzepatide effects with PI3K-AKT inhibition and PPAR pathway activation
    1 context sentence
    Summary · context
    Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.
  8. 08AnimalAnimal study (in vivo)Mechanism

    In aged mice, semaglutide was linked to mitigation of G2/M cell cycle arrest.

    In plain wordsIn aged mice, semaglutide was linked to less G2/M cell cycle arrest.

    Peptide
    Semaglutide
    Outcome
    DecreaseG2/M arrest in aging model
    Study

    mousen: not reported in source

    Aged mouse model
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In the aging model, all three drugs were linked to G2/M arrest mitigation.
    1 context sentence
    Summary · context
    Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.
  9. 09AnimalAnimal study (in vivo)Mechanism

    In aged mice, tirzepatide was linked to mitigation of G2/M cell cycle arrest.

    In plain wordsIn aged mice, tirzepatide was linked to less G2/M cell cycle arrest.

    Peptide
    Tirzepatide
    Outcome
    DecreaseG2/M arrest in aging model
    Study

    mousen: not reported in source

    Aged mouse model
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In the aging model, all three drugs were linked to G2/M arrest mitigation.
    1 context sentence
    Summary · context
    Given the therapeutic potential of GLP-1 receptor agonists (semaglutide, tirzepatide, and retatrutide) in diabetic nephropathy, we evaluated their anti-fibrotic and anti-inflammatory effects in non-diabetic renal fibrosis using HK-2 cells and murine UUO and aging models.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Versions 4 to 39Current

    28 Oct 2026, 02:04 UTC

    The same notice was added 36 times, first on 9 Oct 2026, 19:08 UTC. The status did not change between them.

    Study results updated

  2. Versions 2 to 3

    9 Oct 2026, 03:07 UTC

    The same notice was added 2 times, first on 9 Oct 2026, 03:06 UTC. The status did not change between them.

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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