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Study · Randomized controlled trial · n = 40 · 2025

18 results

Combination metformin and liraglutide in PCOS: clinical efficacy in women and preclinical insights from gut microbiome modulation in rats.

Long XF, Fang YQ, Li YH, Li JY, Wang XP, Wang XL, Zhang L, Liu Y

Frontiers in endocrinology26 Nov 2025

PMID41384017 (opens in a new tab)PMCIDPMC12689399 (opens in a new tab)DOI10.3389/fendo.2025.1599879 (opens in a new tab)PepBankPUB-41384017
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Summary

BackgroundMetformin and liraglutide have been gradually used in the treatment of polycystic ovary syndrome (PCOS) due to their metabolic benefits, but also with some adverse reactions. Evidence suggests that gut microbiota imbalance plays an important role in the pathogenesis of PCOS. This study comprised a clinical trial to evaluate the efficacy of metformin, liraglutide, and their combination in PCOS women, and a parallel animal experiment to explore the potential involvement of gut microbiota.MethodsIn an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks. In a separate animal study, female Sprague-Dawley rats were divided into five groups: (1) PCOS model group (letrozole 1 mg/kg orally); (2) MET group (letrozole + metformin 200 mg/kg orally); (3) LIRA group (letrozole + liraglutide 0.2 mg/kg subcutaneously); (4) COM group (letrozole + metformin + liraglutide at above doses); and (5) healthy controls (no treatment). All treatments lasted 4 weeks.ResultsIn the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio. Notably, body weight, BMI, visceral fat area, and body fat percentage decreased more significantly in the COM group than in the MET group (P<0.05). Compared with the MET group, the COM group was more effective in reducing free testosterone (P=0.01). In the animal experiment, the body weight, estrus cycle, and ovarian morphology of rats in the COM group were significantly improved. Letrozole-induced PCOS rats showed intestinal flora disorder, which was improved by metformin, liraglutide, and their combination by altering the alpha and beta diversity and relative abundance of the gut microbiota.ConclusionMetformin combined with liraglutide significantly improved metabolic and endocrine characteristics in PCOS women. The associated amelioration of gut microbiota dysbiosis in PCOS rats suggests a potential mechanistic link, which warrants verification in future clinical studies.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study18

11 results from studies that gave the peptide. 9 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, adding liraglutide to metformin reduced body weight more than metformin alone (P<0.05).

    In plain wordsIn overweight women with polycystic ovary syndrome, adding liraglutide to metformin lowered body weight more than metformin alone.

    Peptide
    Liraglutide
    Outcome
    DecreaseBody weight, metformin plus liraglutide versus metformin alone
    Study

    n = 40

    Comparator
    Metformin alone
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    1.2 mg once daily · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Notably, body weight, BMI, visceral fat area, and body fat percentage decreased more significantly in the COM group than in the MET group (P<0.05).
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, adding liraglutide to metformin reduced BMI more than metformin alone (P<0.05).

    In plain wordsIn overweight women with polycystic ovary syndrome, adding liraglutide to metformin lowered BMI more than metformin alone.

    Peptide
    Liraglutide
    Outcome
    DecreaseBMI, metformin plus liraglutide versus metformin alone
    Study

    n = 40

    Comparator
    Metformin alone
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    1.2 mg once daily · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Notably, body weight, BMI, visceral fat area, and body fat percentage decreased more significantly in the COM group than in the MET group (P<0.05).
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, adding liraglutide to metformin reduced visceral fat area more than metformin alone (P<0.05).

    In plain wordsIn overweight women with polycystic ovary syndrome, adding liraglutide to metformin cut belly fat more than metformin alone.

    Peptide
    Liraglutide
    Outcome
    DecreaseVisceral fat area, metformin plus liraglutide versus metformin alone
    Study

    n = 40

    Comparator
    Metformin alone
    Outcome group
    Body composition · Metabolic and weight
    Studied dose
    1.2 mg once daily · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Notably, body weight, BMI, visceral fat area, and body fat percentage decreased more significantly in the COM group than in the MET group (P<0.05).
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.
  4. 04HumanRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, adding liraglutide to metformin reduced body fat percentage more than metformin alone (P<0.05).

    In plain wordsIn overweight women with polycystic ovary syndrome, adding liraglutide to metformin lowered body fat percentage more than metformin alone.

    Peptide
    Liraglutide
    Outcome
    DecreaseBody fat percentage, metformin plus liraglutide versus metformin alone
    Study

    n = 40

    Comparator
    Metformin alone
    Outcome group
    Body composition · Metabolic and weight
    Studied dose
    1.2 mg once daily · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Notably, body weight, BMI, visceral fat area, and body fat percentage decreased more significantly in the COM group than in the MET group (P<0.05).
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.
  5. 05HumanRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, adding liraglutide to metformin reduced free testosterone more than metformin alone (P=0.01).

    In plain wordsIn overweight women with polycystic ovary syndrome, adding liraglutide to metformin lowered free testosterone more than metformin alone.

    Peptide
    Liraglutide
    Outcome
    DecreaseFree testosterone, metformin plus liraglutide versus metformin alone
    Study

    n = 40

    Comparator
    Metformin alone
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    1.2 mg once daily · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Compared with the MET group, the COM group was more effective in reducing free testosterone (P=0.01).
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.
  6. 06HumanRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, liraglutide alone reduced body weight (reported as significant).

    In plain wordsIn overweight women with polycystic ovary syndrome, liraglutide alone lowered body weight.

    Peptide
    Liraglutide
    Outcome
    DecreaseBody weight change with liraglutide
    Study

    n = 20

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    1.2 mg once daily · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    In the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio.
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.
  7. 07HumanRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, liraglutide alone reduced blood glucose (reported as significant).

    In plain wordsIn overweight women with polycystic ovary syndrome, liraglutide alone lowered blood glucose.

    Peptide
    Liraglutide
    Outcome
    DecreaseBlood glucose change with liraglutide
    Study

    n = 20

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    1.2 mg once daily · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    In the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio.
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.
  8. 08HumanRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, liraglutide alone reduced blood lipid levels (reported as significant).

    In plain wordsIn overweight women with polycystic ovary syndrome, liraglutide alone lowered blood fat levels.

    Peptide
    Liraglutide
    Outcome
    DecreaseBlood lipid change with liraglutide
    Study

    n = 20

    Outcome group
    Lipids · Metabolic and weight
    Studied dose
    1.2 mg once daily · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    In the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio.
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.
  9. 09HumanRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, liraglutide alone reduced the LH/FSH ratio (reported as significant).

    In plain wordsIn overweight women with polycystic ovary syndrome, liraglutide alone lowered the LH/FSH hormone ratio.

    Peptide
    Liraglutide
    Outcome
    DecreaseLH/FSH ratio change with liraglutide
    Study

    n = 20

    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    1.2 mg once daily · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    In the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio.
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.
  10. 10AnimalAnimal study (in vivo)Efficacy outcome

    In letrozole-induced PCOS rats, liraglutide improved the intestinal flora disorder.

    In plain wordsIn rats with induced polycystic ovary syndrome, liraglutide improved the imbalance of gut bacteria.

    Peptide
    Liraglutide
    Outcome
    Direction not reportedGut microbiota disorder in rats given liraglutide
    Study

    ratn: not reported in source

    Letrozole-induced PCOS model
    Outcome group
    Gut microbiota · Gastrointestinal
    Studied dose
    0.2 mg/kg · subcutaneous · 4 weeksAs given in this study (rat).

    Source sentences

    Summary
    Letrozole-induced PCOS rats showed intestinal flora disorder, which was improved by metformin, liraglutide, and their combination by altering the alpha and beta diversity and relative abundance of the gut microbiota.
    2 context sentences
    Summary · context
    (3) LIRA group (letrozole + liraglutide 0.2 mg/kg subcutaneously)
    Summary · context
    All treatments lasted 4 weeks.
  11. 11AnimalAnimal study (in vivo)Mechanism

    In letrozole-induced PCOS rats, liraglutide altered alpha and beta diversity and the relative abundance of gut microbiota.

    In plain wordsIn rats with induced polycystic ovary syndrome, liraglutide changed the variety and mix of gut bacteria.

    Peptide
    Liraglutide
    Outcome
    Direction not reportedGut microbiota diversity and abundance in rats given liraglutide
    Study

    ratn: not reported in source

    Letrozole-induced PCOS model
    Outcome group
    Gut microbiota · Gastrointestinal
    Studied dose
    0.2 mg/kg · subcutaneous · 4 weeksAs given in this study (rat).

    Source sentences

    Summary
    which was improved by metformin, liraglutide, and their combination by altering the alpha and beta diversity and relative abundance of the gut microbiota.
    2 context sentences
    Summary · context
    (3) LIRA group (letrozole + liraglutide 0.2 mg/kg subcutaneously)
    Summary · context
    All treatments lasted 4 weeks.

Studies that did not test the peptide alone7

In this study, Liraglutide 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 Liraglutide.

  1. 12HumanNot a test of Liraglutide aloneRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, metformin plus liraglutide reduced body weight (reported as significant).

    In plain wordsIn overweight women with polycystic ovary syndrome, metformin plus liraglutide together lowered body weight.

    Peptide
    Liraglutide
    Outcome
    DecreaseBody weight change with metformin plus liraglutide
    Study

    n = 20

    Outcome group
    Body weight · Metabolic and weight

    Source sentences

    Summary
    In the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio.
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.

    In this study, Liraglutide 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 Liraglutide.

  2. 13HumanNot a test of Liraglutide aloneRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, metformin plus liraglutide reduced blood glucose (reported as significant).

    In plain wordsIn overweight women with polycystic ovary syndrome, metformin plus liraglutide together lowered blood glucose.

    Peptide
    Liraglutide
    Outcome
    DecreaseBlood glucose change with metformin plus liraglutide
    Study

    n = 20

    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    In the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio.
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.

    In this study, Liraglutide 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 Liraglutide.

  3. 14HumanNot a test of Liraglutide aloneRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, metformin plus liraglutide reduced blood lipid levels (reported as significant).

    In plain wordsIn overweight women with polycystic ovary syndrome, metformin plus liraglutide together lowered blood fat levels.

    Peptide
    Liraglutide
    Outcome
    DecreaseBlood lipid change with metformin plus liraglutide
    Study

    n = 20

    Outcome group
    Lipids · Metabolic and weight

    Source sentences

    Summary
    In the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio.
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.

    In this study, Liraglutide 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 Liraglutide.

  4. 15HumanNot a test of Liraglutide aloneRandomized controlled trialEfficacy outcome

    In overweight or obese women with PCOS, metformin plus liraglutide reduced the LH/FSH ratio (reported as significant).

    In plain wordsIn overweight women with polycystic ovary syndrome, metformin plus liraglutide together lowered the LH/FSH hormone ratio.

    Peptide
    Liraglutide
    Outcome
    DecreaseLH/FSH ratio change with metformin plus liraglutide
    Study

    n = 20

    Outcome group
    Sex hormones and fertility · Endocrine and hormones

    Source sentences

    Summary
    In the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio.
    1 context sentence
    Summary · context
    In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks.

    In this study, Liraglutide 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 Liraglutide.

  5. 16AnimalNot a test of Liraglutide aloneAnimal study (in vivo)Efficacy outcome

    In letrozole-induced PCOS rats, metformin plus liraglutide significantly improved body weight.

    In plain wordsIn rats with induced polycystic ovary syndrome, metformin plus liraglutide together improved body weight.

    Peptide
    Liraglutide
    Outcome
    Direction not reportedBody weight in rats given metformin plus liraglutide
    Study

    ratn: not reported in source

    Letrozole-induced PCOS model
    Outcome group
    Body weight · Metabolic and weight

    Source sentences

    Summary
    In the animal experiment, the body weight, estrus cycle, and ovarian morphology of rats in the COM group were significantly improved.
    2 context sentences
    Summary · context
    (4) COM group (letrozole + metformin + liraglutide at above doses)
    Summary · context
    All treatments lasted 4 weeks.

    In this study, Liraglutide 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 Liraglutide.

  6. 17AnimalNot a test of Liraglutide aloneAnimal study (in vivo)Efficacy outcome

    In letrozole-induced PCOS rats, metformin plus liraglutide significantly improved the estrus cycle.

    In plain wordsIn rats with induced polycystic ovary syndrome, metformin plus liraglutide together improved the estrus cycle.

    Peptide
    Liraglutide
    Outcome
    Direction not reportedEstrus cycle in rats given metformin plus liraglutide
    Study

    ratn: not reported in source

    Letrozole-induced PCOS model
    Outcome group
    Sex hormones and fertility · Reproductive and sexual health

    Source sentences

    Summary
    In the animal experiment, the body weight, estrus cycle, and ovarian morphology of rats in the COM group were significantly improved.
    2 context sentences
    Summary · context
    (4) COM group (letrozole + metformin + liraglutide at above doses)
    Summary · context
    All treatments lasted 4 weeks.

    In this study, Liraglutide 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 Liraglutide.

  7. 18AnimalNot a test of Liraglutide aloneAnimal study (in vivo)Efficacy outcome

    In letrozole-induced PCOS rats, metformin plus liraglutide significantly improved ovarian morphology.

    In plain wordsIn rats with induced polycystic ovary syndrome, metformin plus liraglutide together improved the look of the ovaries under the microscope.

    Peptide
    Liraglutide
    Outcome
    Direction not reportedOvarian morphology in rats given metformin plus liraglutide
    Study

    ratn: not reported in source

    Letrozole-induced PCOS model
    Outcome group
    Sex hormones and fertility · Reproductive and sexual health

    Source sentences

    Summary
    In the animal experiment, the body weight, estrus cycle, and ovarian morphology of rats in the COM group were significantly improved.
    2 context sentences
    Summary · context
    (4) COM group (letrozole + metformin + liraglutide at above doses)
    Summary · context
    All treatments lasted 4 weeks.

    In this study, Liraglutide 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 Liraglutide.

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. Version 2Current

    12 Oct 2026, 11:11 UTC

    Study results updated

  2. 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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