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

37 results

Efficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison.

Hitaka K, Sugawara T, Matsumoto M, Nio Y

International journal of obesity (2005)21 Feb 2026Cited by 1 (Europe PMC)

Summary

IntroductionMelanocortin 4 receptor (MC4R) is a G-protein-coupled receptor expressed in the hypothalamus, playing a key role in regulating feeding behavior and energy homeostasis. MC4R is integral to the POMC-MC4R and leptin-MC4R pathways, which control food intake and body weight. Mutations in the POMC gene lead to severe early-onset obesity and increased food consumption. Recently, glucagon-like peptide-1 (GLP-1) analogs, including semaglutide, tirzepatide, and retatrutide, have been explored as potential anti-obesity therapies.MethodsThis study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway. GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.ResultsThe percentage of body weight reduction was 19.7 ± 4.1% for semaglutide, 31.6 ± 7.6% for tirzepatide, and 24.1 ± 5.8% for retatrutide. Body composition analysis, including fat and lean mass, was performed using the Echo-MRI system, revealing significant suppression of both fat and lean mass by all three GLP-1 analogs. Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy. While GLP-1 analogs suppressed genes related to fatty acid synthesis, they had no significant effect on inflammation-related gene expressions. Additionally, GLP-1 analogs reduced energy expenditure, with only tirzepatide showing a significant decrease in the respiratory quotient (RQ) in MC4R KO mice.ConclusionOur findings demonstrate that all three GLP-1 analogs, semaglutide, tirzepatide, and retatrutide, exhibit significant anti-obesity effects in MC4R KO mice. These results suggest that GLP-1 analogs may provide an effective treatment option for patients with MC4R-POMC pathway deficiencies. Moreover, the efficacy of these drugs in MC4R KO mice aligns with clinical studies, indicating that MC4R KO mice serve as a reliable animal model for obesity research.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study37

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, retatrutide reduced body weight by 24.1 ± 5.8% after 21 days.

    In plain wordsIn mice lacking MC4R, retatrutide lowered body weight.

    Outcome
    DecreaseBody weight reduction
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Measurements

    Body weight reduction
    24.1%
    retatrutide

    Source sentences

    Summary
    The percentage of body weight reduction was 19.7 ± 4.1% for semaglutide, 31.6 ± 7.6% for tirzepatide, and 24.1 ± 5.8% for retatrutide.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, retatrutide, like semaglutide and tirzepatide, significantly suppressed fat mass.

    In plain wordsIn mice lacking MC4R, retatrutide lowered fat mass.

    Outcome
    DecreaseFat mass
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Source sentences

    Summary
    Body composition analysis, including fat and lean mass, was performed using the Echo-MRI system, revealing significant suppression of both fat and lean mass by all three GLP-1 analogs.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, retatrutide, like semaglutide and tirzepatide, significantly suppressed lean mass.

    In plain wordsIn mice lacking MC4R, retatrutide also lowered lean mass.

    Outcome
    DecreaseLean mass
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Source sentences

    Summary
    Body composition analysis, including fat and lean mass, was performed using the Echo-MRI system, revealing significant suppression of both fat and lean mass by all three GLP-1 analogs.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, retatrutide did not significantly decrease the respiratory quotient; only tirzepatide did.

    In plain wordsIn mice lacking MC4R, retatrutide did not significantly change the respiratory quotient; tirzepatide did.

    Outcome
    No significant changeRespiratory quotient
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Energy expenditure and thermogenesis · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Source sentences

    Summary
    Additionally, GLP-1 analogs reduced energy expenditure, with only tirzepatide showing a significant decrease in the respiratory quotient (RQ) in MC4R KO mice.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, semaglutide reduced body weight by 19.7 ± 4.1% over 21 days.

    In plain wordsIn mice lacking the MC4R gene, semaglutide lowered body weight over 21 days.

    Outcome
    DecreaseBody weight reduction
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Measurements

    Body weight reduction
    19.7%
    semaglutide

    Source sentences

    Summary
    The percentage of body weight reduction was 19.7 ± 4.1% for semaglutide, 31.6 ± 7.6% for tirzepatide, and 24.1 ± 5.8% for retatrutide.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  6. 06AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, tirzepatide reduced body weight by 31.6 ± 7.6% over 21 days.

    In plain wordsIn mice lacking the MC4R gene, tirzepatide lowered body weight over 21 days.

    Outcome
    DecreaseBody weight reduction
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Measurements

    Body weight reduction
    31.6%
    tirzepatide

    Source sentences

    Summary
    The percentage of body weight reduction was 19.7 ± 4.1% for semaglutide, 31.6 ± 7.6% for tirzepatide, and 24.1 ± 5.8% for retatrutide.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  7. 07AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, semaglutide significantly suppressed fat mass on Echo-MRI.

    In plain wordsIn mice lacking the MC4R gene, semaglutide lowered fat mass.

    Outcome
    DecreaseFat mass
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Source sentences

    Summary
    Body composition analysis, including fat and lean mass, was performed using the Echo-MRI system, revealing significant suppression of both fat and lean mass by all three GLP-1 analogs.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  8. 08AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, tirzepatide significantly suppressed fat mass on Echo-MRI.

    In plain wordsIn mice lacking the MC4R gene, tirzepatide lowered fat mass.

    Outcome
    DecreaseFat mass
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Source sentences

    Summary
    Body composition analysis, including fat and lean mass, was performed using the Echo-MRI system, revealing significant suppression of both fat and lean mass by all three GLP-1 analogs.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  9. 09AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, semaglutide significantly suppressed lean mass on Echo-MRI.

    In plain wordsIn mice lacking the MC4R gene, semaglutide also lowered lean mass.

    Outcome
    DecreaseLean mass
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Source sentences

    Summary
    Body composition analysis, including fat and lean mass, was performed using the Echo-MRI system, revealing significant suppression of both fat and lean mass by all three GLP-1 analogs.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  10. 10AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, tirzepatide significantly suppressed lean mass on Echo-MRI.

    In plain wordsIn mice lacking the MC4R gene, tirzepatide also lowered lean mass.

    Outcome
    DecreaseLean mass
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Source sentences

    Summary
    Body composition analysis, including fat and lean mass, was performed using the Echo-MRI system, revealing significant suppression of both fat and lean mass by all three GLP-1 analogs.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  11. 11AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, semaglutide did not significantly change the respiratory quotient; only tirzepatide did.

    In plain wordsIn mice lacking the MC4R gene, semaglutide did not clearly change the respiratory quotient.

    Outcome
    No significant changeRespiratory quotient
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Source sentences

    Summary
    Additionally, GLP-1 analogs reduced energy expenditure, with only tirzepatide showing a significant decrease in the respiratory quotient (RQ) in MC4R KO mice.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.
  12. 12AnimalAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, tirzepatide significantly decreased the respiratory quotient; the other analogs did not.

    In plain wordsIn mice lacking the MC4R gene, tirzepatide lowered the respiratory quotient, a measure of fuel use.

    Outcome
    DecreaseRespiratory quotient
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 21 daysAs given in this study (mouse).

    Source sentences

    Summary
    Additionally, GLP-1 analogs reduced energy expenditure, with only tirzepatide showing a significant decrease in the respiratory quotient (RQ) in MC4R KO mice.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

Studies that did not test the peptide alone25

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

  1. 13AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including retatrutide improved plasma insulin levels.

    In plain wordsIn mice lacking MC4R, retatrutide improved plasma insulin levels.

    Outcome
    Direction not reportedPlasma insulin
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.

  2. 14AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including retatrutide improved HOMA-IR.

    In plain wordsIn mice lacking MC4R, retatrutide improved an insulin resistance score.

    Outcome
    DecreaseHOMA-IR
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.

  3. 15AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including retatrutide improved cholesterol levels.

    In plain wordsIn mice lacking MC4R, retatrutide improved cholesterol levels.

    Outcome
    Direction not reportedCholesterol
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Lipids · Metabolic and weight

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.

  4. 16AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including retatrutide improved the liver damage marker AST.

    In plain wordsIn mice lacking MC4R, retatrutide improved a blood marker of liver damage (AST).

    Outcome
    DecreaseAST
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Liver fat and liver function · Liver

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.

  5. 17AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including retatrutide improved the liver damage marker ALT.

    In plain wordsIn mice lacking MC4R, retatrutide improved a blood marker of liver damage (ALT).

    Outcome
    DecreaseALT
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Liver fat and liver function · Liver

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.

  6. 18AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including retatrutide reduced liver hypertrophy.

    In plain wordsIn mice lacking MC4R, retatrutide reduced liver enlargement.

    Outcome
    DecreaseLiver hypertrophy
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Liver fat and liver function · Liver

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.

  7. 19AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Mechanism

    In MC4R knockout mice, GLP-1 analogs including retatrutide suppressed genes related to fatty acid synthesis.

    In plain wordsIn mice lacking MC4R, retatrutide lowered activity of genes linked to fat production.

    Outcome
    DecreaseFatty acid synthesis gene expression
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Gene expression · Metabolic and weight

    Source sentences

    Summary
    While GLP-1 analogs suppressed genes related to fatty acid synthesis, they had no significant effect on inflammation-related gene expressions.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.

  8. 20AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Mechanism

    In MC4R knockout mice, GLP-1 analogs including retatrutide had no significant effect on inflammation-related gene expression.

    In plain wordsIn mice lacking MC4R, retatrutide did not significantly change activity of inflammation genes.

    Outcome
    No significant changeInflammation-related gene expression
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Inflammation markers · Immune and inflammation

    Source sentences

    Summary
    While GLP-1 analogs suppressed genes related to fatty acid synthesis, they had no significant effect on inflammation-related gene expressions.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.

  9. 21AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including retatrutide reduced energy expenditure.

    In plain wordsIn mice lacking MC4R, retatrutide lowered energy expenditure.

    Outcome
    DecreaseEnergy expenditure
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Energy expenditure and thermogenesis · Metabolic and weight

    Source sentences

    Summary
    Additionally, GLP-1 analogs reduced energy expenditure, with only tirzepatide showing a significant decrease in the respiratory quotient (RQ) in MC4R KO mice.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.

  10. 22AnimalNot a test of Semaglutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including semaglutide improved plasma insulin levels.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including semaglutide improved plasma insulin levels.

    Outcome
    Direction not reportedPlasma insulin
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  11. 23AnimalNot a test of Tirzepatide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including tirzepatide improved plasma insulin levels.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including tirzepatide improved plasma insulin levels.

    Outcome
    Direction not reportedPlasma insulin
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  12. 24AnimalNot a test of Semaglutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including semaglutide improved HOMA-IR.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including semaglutide improved a measure of insulin resistance.

    Outcome
    Direction not reportedHOMA-IR
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  13. 25AnimalNot a test of Tirzepatide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including tirzepatide improved HOMA-IR.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including tirzepatide improved a measure of insulin resistance.

    Outcome
    Direction not reportedHOMA-IR
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  14. 26AnimalNot a test of Semaglutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including semaglutide improved cholesterol levels.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including semaglutide improved cholesterol levels.

    Outcome
    Direction not reportedCholesterol
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Lipids · Metabolic and weight

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  15. 27AnimalNot a test of Tirzepatide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including tirzepatide improved cholesterol levels.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including tirzepatide improved cholesterol levels.

    Outcome
    Direction not reportedCholesterol
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Lipids · Metabolic and weight

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  16. 28AnimalNot a test of Semaglutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including semaglutide improved the liver damage markers AST and ALT.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including semaglutide improved blood markers of liver damage.

    Outcome
    Direction not reportedLiver damage markers (AST and ALT)
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Liver fat and liver function · Liver

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  17. 29AnimalNot a test of Tirzepatide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including tirzepatide improved the liver damage markers AST and ALT.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including tirzepatide improved blood markers of liver damage.

    Outcome
    Direction not reportedLiver damage markers (AST and ALT)
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Liver fat and liver function · Liver

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  18. 30AnimalNot a test of Semaglutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including semaglutide reduced liver hypertrophy.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including semaglutide reduced liver enlargement.

    Outcome
    DecreaseLiver hypertrophy
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Liver fat and liver function · Liver

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  19. 31AnimalNot a test of Tirzepatide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including tirzepatide reduced liver hypertrophy.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including tirzepatide reduced liver enlargement.

    Outcome
    DecreaseLiver hypertrophy
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Liver fat and liver function · Liver

    Source sentences

    Summary
    Furthermore, GLP-1 analogs improved plasma insulin levels, HOMA-IR, cholesterol levels, and markers of liver damage (AST and ALT), as well as reduced liver hypertrophy.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  20. 32AnimalNot a test of Semaglutide aloneAnimal study (in vivo)Mechanism

    In MC4R knockout mice, GLP-1 analogs including semaglutide suppressed genes related to fatty acid synthesis.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including semaglutide lowered activity of fat-making genes.

    Outcome
    DecreaseExpression of fatty acid synthesis genes
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Liver fat and liver function · Metabolic and weight

    Source sentences

    Summary
    While GLP-1 analogs suppressed genes related to fatty acid synthesis, they had no significant effect on inflammation-related gene expressions.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  21. 33AnimalNot a test of Tirzepatide aloneAnimal study (in vivo)Mechanism

    In MC4R knockout mice, GLP-1 analogs including tirzepatide suppressed genes related to fatty acid synthesis.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including tirzepatide lowered activity of fat-making genes.

    Outcome
    DecreaseExpression of fatty acid synthesis genes
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Liver fat and liver function · Metabolic and weight

    Source sentences

    Summary
    While GLP-1 analogs suppressed genes related to fatty acid synthesis, they had no significant effect on inflammation-related gene expressions.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  22. 34AnimalNot a test of Semaglutide aloneAnimal study (in vivo)Mechanism

    In MC4R knockout mice, GLP-1 analogs including semaglutide had no significant effect on inflammation-related gene expression.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including semaglutide did not clearly change inflammation-related genes.

    Outcome
    No significant changeExpression of inflammation-related genes
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Inflammation markers · Immune and inflammation

    Source sentences

    Summary
    While GLP-1 analogs suppressed genes related to fatty acid synthesis, they had no significant effect on inflammation-related gene expressions.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  23. 35AnimalNot a test of Tirzepatide aloneAnimal study (in vivo)Mechanism

    In MC4R knockout mice, GLP-1 analogs including tirzepatide had no significant effect on inflammation-related gene expression.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including tirzepatide did not clearly change inflammation-related genes.

    Outcome
    No significant changeExpression of inflammation-related genes
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Inflammation markers · Immune and inflammation

    Source sentences

    Summary
    While GLP-1 analogs suppressed genes related to fatty acid synthesis, they had no significant effect on inflammation-related gene expressions.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  24. 36AnimalNot a test of Semaglutide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including semaglutide reduced energy expenditure.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including semaglutide lowered energy expenditure.

    Outcome
    DecreaseEnergy expenditure
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight

    Source sentences

    Summary
    Additionally, GLP-1 analogs reduced energy expenditure, with only tirzepatide showing a significant decrease in the respiratory quotient (RQ) in MC4R KO mice.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  25. 37AnimalNot a test of Tirzepatide aloneAnimal study (in vivo)Efficacy outcome

    In MC4R knockout mice, GLP-1 analogs including tirzepatide reduced energy expenditure.

    In plain wordsIn mice lacking the MC4R gene, GLP-1 drugs including tirzepatide lowered energy expenditure.

    Outcome
    DecreaseEnergy expenditure
    Study

    mousen: not reported in source

    MC4R knockout mice
    Outcome group
    Body weight · Metabolic and weight

    Source sentences

    Summary
    Additionally, GLP-1 analogs reduced energy expenditure, with only tirzepatide showing a significant decrease in the respiratory quotient (RQ) in MC4R KO mice.
    2 context sentences
    Summary · context
    This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway.
    Summary · context
    GLP-1 analogs were administered for 21 days to MC4R KO mice and compared their efficacy.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

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, 18:17 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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