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Study · Systematic review · 2026

9 results

Weight Loss With GLP-1 Agonists in Nondiabetic Adults: Systematic Review and Network Meta-Analysis.

Lim M, Gokhale P, Akosah A, Villa-Zapata L

Obesity (Silver Spring, Md.)5 Apr 2026Cited by 1 (Europe PMC)

PMID41936548 (opens in a new tab)DOI10.1002/oby.70169 (opens in a new tab)PepBankPUB-41936548
Publisher pagePubMedAsk about this study
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Summary

ObjectiveTwo glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus. This systematic review and network meta-analysis aims to compare the efficacy of these agents against each other.MethodsA comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025. Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included. A frequentist random-effects network meta-analysis was performed using R 4.3.3.ResultsOf 1420 articles identified, 15 RCTs with 14,059 patients were included. All agents significantly reduced body weight compared to placebo. The largest reduction occurred with the maximum tolerated dose of tirzepatide, followed by tirzepatide 15 mg and 10 mg, semaglutide 2.4 mg, tirzepatide 5 mg, and liraglutide 3 mg. Tirzepatide and semaglutide were associated with a higher risk of any adverse event compared with placebo, whereas liraglutide was not.ConclusionsTirzepatide, particularly at higher doses, provides the greatest weight reduction in adults without diabetes. Future studies should evaluate discontinuation, weight regain, metabolic outcomes, cost-effectiveness, and patient preferences.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

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

  1. 01HumanSystematic reviewEfficacy outcome

    In adults with obesity without type 2 diabetes, liraglutide 3 mg significantly reduced body weight versus placebo.

    In plain wordsIn adults with obesity without type 2 diabetes, liraglutide 3 mg reduced body weight versus placebo.

    Peptide
    Liraglutide
    Outcome
    DecreaseBody weight
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    3 mgAs given in this study (human).

    Source sentences

    Summary
    All agents significantly reduced body weight compared to placebo.
    5 context sentences
    Summary · context
    The largest reduction occurred with the maximum tolerated dose of tirzepatide, followed by tirzepatide 15 mg and 10 mg, semaglutide 2.4 mg, tirzepatide 5 mg, and liraglutide 3 mg.
    Summary · context
    Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus.
    Summary · context
    A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025.
    Summary · context
    Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included.
    Summary · context
    A frequentist random-effects network meta-analysis was performed using R 4.3.3.
  2. 02HumanSystematic reviewEfficacy outcome

    In adults with obesity without type 2 diabetes, semaglutide 2.4 mg significantly reduced body weight versus placebo.

    In plain wordsIn adults with obesity without type 2 diabetes, semaglutide 2.4 mg reduced body weight versus placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseBody weight
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    2.4 mgAs given in this study (human).

    Source sentences

    Summary
    All agents significantly reduced body weight compared to placebo.
    5 context sentences
    Summary · context
    The largest reduction occurred with the maximum tolerated dose of tirzepatide, followed by tirzepatide 15 mg and 10 mg, semaglutide 2.4 mg, tirzepatide 5 mg, and liraglutide 3 mg.
    Summary · context
    Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus.
    Summary · context
    A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025.
    Summary · context
    Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included.
    Summary · context
    A frequentist random-effects network meta-analysis was performed using R 4.3.3.
  3. 03HumanSystematic reviewEfficacy outcome

    In adults with obesity without type 2 diabetes, maximum-tolerated-dose tirzepatide had the largest body-weight reduction versus placebo.

    In plain wordsIn adults with obesity without type 2 diabetes, maximum-tolerated-dose tirzepatide reduced body weight versus placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight at maximum tolerated dose
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    All agents significantly reduced body weight compared to placebo.
    5 context sentences
    Summary · context
    The largest reduction occurred with the maximum tolerated dose of tirzepatide, followed by tirzepatide 15 mg and 10 mg, semaglutide 2.4 mg, tirzepatide 5 mg, and liraglutide 3 mg.
    Summary · context
    Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus.
    Summary · context
    A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025.
    Summary · context
    Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included.
    Summary · context
    A frequentist random-effects network meta-analysis was performed using R 4.3.3.
  4. 04HumanSystematic reviewEfficacy outcome

    In adults with obesity without type 2 diabetes, tirzepatide 15 mg significantly reduced body weight versus placebo.

    In plain wordsIn adults with obesity without type 2 diabetes, tirzepatide 15 mg reduced body weight versus placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    15 mgAs given in this study (human).

    Source sentences

    Summary
    All agents significantly reduced body weight compared to placebo.
    5 context sentences
    Summary · context
    The largest reduction occurred with the maximum tolerated dose of tirzepatide, followed by tirzepatide 15 mg and 10 mg, semaglutide 2.4 mg, tirzepatide 5 mg, and liraglutide 3 mg.
    Summary · context
    Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus.
    Summary · context
    A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025.
    Summary · context
    Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included.
    Summary · context
    A frequentist random-effects network meta-analysis was performed using R 4.3.3.
  5. 05HumanSystematic reviewEfficacy outcome

    In adults with obesity without type 2 diabetes, tirzepatide 10 mg significantly reduced body weight versus placebo.

    In plain wordsIn adults with obesity without type 2 diabetes, tirzepatide 10 mg reduced body weight versus placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    10 mgAs given in this study (human).

    Source sentences

    Summary
    All agents significantly reduced body weight compared to placebo.
    5 context sentences
    Summary · context
    The largest reduction occurred with the maximum tolerated dose of tirzepatide, followed by tirzepatide 15 mg and 10 mg, semaglutide 2.4 mg, tirzepatide 5 mg, and liraglutide 3 mg.
    Summary · context
    Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus.
    Summary · context
    A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025.
    Summary · context
    Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included.
    Summary · context
    A frequentist random-effects network meta-analysis was performed using R 4.3.3.
  6. 06HumanSystematic reviewEfficacy outcome

    In adults with obesity without type 2 diabetes, tirzepatide 5 mg significantly reduced body weight versus placebo.

    In plain wordsIn adults with obesity without type 2 diabetes, tirzepatide 5 mg reduced body weight versus placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    5 mgAs given in this study (human).

    Source sentences

    Summary
    All agents significantly reduced body weight compared to placebo.
    5 context sentences
    Summary · context
    The largest reduction occurred with the maximum tolerated dose of tirzepatide, followed by tirzepatide 15 mg and 10 mg, semaglutide 2.4 mg, tirzepatide 5 mg, and liraglutide 3 mg.
    Summary · context
    Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus.
    Summary · context
    A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025.
    Summary · context
    Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included.
    Summary · context
    A frequentist random-effects network meta-analysis was performed using R 4.3.3.
  7. 07HumanSystematic reviewSafety outcome

    In adults with obesity without type 2 diabetes, liraglutide was not associated with a higher risk of any adverse event versus placebo.

    In plain wordsIn adults with obesity without type 2 diabetes, liraglutide was not associated with higher adverse-event risk versus placebo.

    Peptide
    Liraglutide
    Outcome
    Not applicableAny adverse event
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Tirzepatide and semaglutide were associated with a higher risk of any adverse event compared with placebo, whereas liraglutide was not.
    4 context sentences
    Summary · context
    Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus.
    Summary · context
    A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025.
    Summary · context
    Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included.
    Summary · context
    A frequentist random-effects network meta-analysis was performed using R 4.3.3.
  8. 08HumanSystematic reviewSafety outcome

    In adults with obesity without type 2 diabetes, semaglutide was associated with a higher risk of any adverse event versus placebo.

    In plain wordsIn adults with obesity without type 2 diabetes, semaglutide had more adverse events than placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseAny adverse event
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Tirzepatide and semaglutide were associated with a higher risk of any adverse event compared with placebo, whereas liraglutide was not.
    4 context sentences
    Summary · context
    Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus.
    Summary · context
    A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025.
    Summary · context
    Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included.
    Summary · context
    A frequentist random-effects network meta-analysis was performed using R 4.3.3.
  9. 09HumanSystematic reviewSafety outcome

    In adults with obesity without type 2 diabetes, tirzepatide was associated with a higher risk of any adverse event versus placebo.

    In plain wordsIn adults with obesity without type 2 diabetes, tirzepatide had more adverse events than placebo.

    Peptide
    Tirzepatide
    Outcome
    IncreaseAny adverse event
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Tirzepatide and semaglutide were associated with a higher risk of any adverse event compared with placebo, whereas liraglutide was not.
    4 context sentences
    Summary · context
    Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus.
    Summary · context
    A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025.
    Summary · context
    Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included.
    Summary · context
    A frequentist random-effects network meta-analysis was performed using R 4.3.3.

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 4Current

    12 Oct 2026, 11:11 UTC

    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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