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Study · Randomized controlled trial · 2021

6 results

Liraglutide and sitagliptin have no effect on intestinal microbiota composition: A 12-week randomized placebo-controlled trial in adults with type 2 diabetes.

Smits MM, Fluitman KS, Herrema H, Davids M, Kramer MHH, Groen AK, Belzer C, de Vos WM, Cahen DL, Nieuwdorp M, van Raalte DH

Diabetes & metabolism8 Jan 2021Cited by 59 (Europe PMC)

PMID33429063 (opens in a new tab)DOI10.1016/j.diabet.2021.101223 (opens in a new tab)PepBankPUB-33429063
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Summary

AimPreclinical data suggest that treatment with either glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors could change the intestinal microbiome and thereby contribute to their beneficial (cardio)metabolic effects. Therefore, our study aimed to investigate the effects of these agents on microbiota composition in adults with type 2 diabetes (T2D).MethodsA total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m2, HbA1c 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial. Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks. Faecal samples were collected at baseline and at 12 weeks after the start of the intervention. Microbiota analyses were performed by 16S rRNA gene-sequencing analysis. Bile acids were measured in faeces and plasma.ResultsLiraglutide decreased HbA1c by 1.3% (95% CI: -1.7 to -0.9) and tended to reduce body weight (-1.7 kg, 95% CI: -3.6 to 0.3), but increased faecal secondary bile acid deoxycholic acid. Sitagliptin lowered HbA1c by 0.8% (95% CI: -1.4 to -0.4) while body weight remained stable (-0.8 kg, 95% CI: -2.7 to 1.0), but increased faecal levels of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid. However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters.ConclusionThese data suggest that the beneficial effects of liraglutide and sitagliptin on glucose metabolism, body weight and bile acids, when used as add-on therapies to metformin or sulphonylureas, are not linked to changes in the intestinal microbiota (NCT01744236).
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes on metformin and/or sulphonylureas, 12 weeks of liraglutide decreased HbA1c by 1.3%.

    In plain wordsIn adults with type 2 diabetes, liraglutide lowered HbA1c (long-term blood sugar) over 12 weeks.

    Peptide
    Liraglutide
    Outcome
    DecreaseHbA1c change
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    1.8 mg · subcutaneous · 12 weeksAs given in this study (human).

    Measurements

    HbA1c change
    −1.3%
    liraglutide 1.8 mg

    Source sentences

    Summary
    Liraglutide decreased HbA1c by 1.3% (95% CI: -1.7 to -0.9)
    2 context sentences
    Summary · context
    A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m2, HbA1c 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial.
    Summary · context
    Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes, liraglutide tended to reduce body weight over 12 weeks, but the confidence interval included zero.

    In plain wordsIn adults with type 2 diabetes, liraglutide only tended to lower body weight over 12 weeks; the change was not clear.

    Peptide
    Liraglutide
    Outcome
    No significant changeBody weight change
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    1.8 mg · subcutaneous · 12 weeksAs given in this study (human).

    Measurements

    Body weight change
    −1.7 kg
    liraglutide 1.8 mg

    Source sentences

    Summary
    tended to reduce body weight (-1.7 kg, 95% CI: -3.6 to 0.3)
    2 context sentences
    Summary · context
    A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m2, HbA1c 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial.
    Summary · context
    Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks.
  3. 03HumanRandomized controlled trialMechanism

    In adults with type 2 diabetes, liraglutide increased faecal levels of the secondary bile acid deoxycholic acid.

    In plain wordsIn adults with type 2 diabetes, liraglutide raised the amount of the bile acid deoxycholic acid in stool.

    Peptide
    Liraglutide
    Outcome
    IncreaseFaecal deoxycholic acid
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Gastrointestinal
    Studied dose
    1.8 mg · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    increased faecal secondary bile acid deoxycholic acid.
    2 context sentences
    Summary · context
    A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m2, HbA1c 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial.
    Summary · context
    Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks.
  4. 04HumanRandomized controlled trialMechanism

    In adults with type 2 diabetes, liraglutide did not affect alpha diversity of the intestinal microbiota.

    In plain wordsIn adults with type 2 diabetes, liraglutide did not change the variety of gut bacteria within a person.

    Peptide
    Liraglutide
    Outcome
    No significant changeIntestinal microbiota alpha diversity
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Gastrointestinal
    Studied dose
    1.8 mg · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters.
    2 context sentences
    Summary · context
    A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m2, HbA1c 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial.
    Summary · context
    Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks.
  5. 05HumanRandomized controlled trialMechanism

    In adults with type 2 diabetes, liraglutide did not affect beta diversity of the intestinal microbiota.

    In plain wordsIn adults with type 2 diabetes, liraglutide did not change how gut bacteria differed between people.

    Peptide
    Liraglutide
    Outcome
    No significant changeIntestinal microbiota beta diversity
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Gastrointestinal
    Studied dose
    1.8 mg · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters.
    2 context sentences
    Summary · context
    A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m2, HbA1c 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial.
    Summary · context
    Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks.
  6. 06HumanRandomized controlled trialMechanism

    In adults with type 2 diabetes, changes in microbial composition with liraglutide were not related to clinical parameters.

    In plain wordsIn adults with type 2 diabetes, changes in gut bacteria with liraglutide were not linked to clinical measures.

    Peptide
    Liraglutide
    Outcome
    No significant changeAssociation of microbial composition change with clinical parameters
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Gastrointestinal
    Studied dose
    1.8 mg · subcutaneous · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters.
    2 context sentences
    Summary · context
    A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m2, HbA1c 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial.
    Summary · context
    Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks.

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

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 4NCT01744236

SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

Amsterdam UMC, location VUmcn = 70Apr 2013 to Aug 2015

Type 2 Diabetes

Trial pageClinicalTrials.govUpdated 9 Dec 2015

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, 03:05 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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