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Study · Systematic review · n = 6,266 · 2025

6 results

Weight Loss Efficacy of Tirzepatide Compared to Placebo or GLP-1 Receptor Agonists in Adults With Obesity or Overweight: A Meta-Analysis of Randomized Controlled Trials With ≥ 20 Weeks Treatment Duration.

Khawaji A, A Jaly A, A Bakri H, Ravi R, Hattan A, Khawaji A, Najmi W

Journal of obesity24 Jul 2025Cited by 7 (Europe PMC)

PMID40746703 (opens in a new tab)PMCIDPMC12313391 (opens in a new tab)DOI10.1155/jobe/3442754 (opens in a new tab)PepBankPUB-40746703
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Summary

Introduction: Tirzepatide, a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like Peptide 1 (GLP-1) analogue, is a novel medication with comparable pharmacological characteristics and has demonstrated promising weight reduction outcomes in its antidiabetic trials following the approval of liraglutide and semaglutide for long-term weight control. Nonetheless, this efficacy has not been fully explored, so this meta-analysis was aimed to measure the weight loss efficacy and safety of tirzepatide in adults with overweight or obesity. Methods: We searched the PubMed, Cochrane, and Embase databases for RCTs of once-weekly tirzepatide vs. placebo or GLP-1 receptor agonists. We included studies involving adult participants who were overweight or obese despite T2DM or OHA use, with a trial duration of at least 20 weeks. The primary outcomes accounted for the mean difference in weight from baseline in the three doses of tirzepatide compared to placebo and GLP-1 receptor agonists, separately. The secondary outcomes included safety profiles and achievement of categorical weight loss of 5%, 10% and 15%. We performed the statistical analysis on RevMan 5.4, GRADE assessment using GRADEpro GDT and the quality of the included studies assessed using the Cochrane risk-of-bias (Version 2) tool. Results: We identified six RCTs in which the data of 6266 subjects were analysed. Once-weekly doses (5, 10 and 15 mg) of tirzepatide were more effective than placebo and GLP-1 RAs. Also, the proportion of patients achieving categorical weight loss goals was higher in the tirzepatide groups than in others. GRADE assessment also indicated high-certainty evidence for ≥ 15% weight loss with tirzepatide and moderate-to-low certainty for lower thresholds. Gastrointestinal side effects appeared similar between the three doses of tirzepatide and GLP-1 RAs, but they were significantly higher than placebo might impact tolerability for certain patients. Conclusion: A dose-dependent tirzepatide was superior to placebo and GLP-1 RAs in weight reduction. However, the lean mass reduction and tolerability require further investigation. Trial Registration: ClinicalTrials.gov identifier: NCT04255433.
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. 01HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, once-weekly tirzepatide at 5, 10 and 15 mg was more effective than placebo for weight reduction.

    In plain wordsIn adults with overweight or obesity, tirzepatide was more effective than placebo for weight loss at all three weekly doses.

    Peptide
    Tirzepatide
    Outcome
    DecreaseWeight change versus placebo
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Primary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    5, 10 and 15 mg once weekly · at least 20 weeksAs given in this study (human).

    Source sentences

    Summary
    Once-weekly doses (5, 10 and 15 mg) of tirzepatide were more effective than placebo and GLP-1 RAs.
    3 context sentences
    Summary · context
    We searched the PubMed, Cochrane, and Embase databases for RCTs of once-weekly tirzepatide vs. placebo or GLP-1 receptor agonists.
    Summary · context
    We included studies involving adult participants who were overweight or obese despite T2DM or OHA use, with a trial duration of at least 20 weeks.
    Summary · context
    We identified six RCTs in which the data of 6266 subjects were analysed.
  2. 02HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, once-weekly tirzepatide at 5, 10 and 15 mg was more effective than GLP-1 receptor agonists for weight reduction.

    In plain wordsIn adults with overweight or obesity, tirzepatide was more effective than other GLP-1 drugs for weight loss at all three weekly doses.

    Peptide
    Tirzepatide
    Outcome
    DecreaseWeight change versus GLP-1 receptor agonists
    Study

    n: not reported in source

    Comparator
    GLP-1 receptor agonists
    Analysis
    Primary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    5, 10 and 15 mg once weekly · at least 20 weeksAs given in this study (human).

    Source sentences

    Summary
    Once-weekly doses (5, 10 and 15 mg) of tirzepatide were more effective than placebo and GLP-1 RAs.
    3 context sentences
    Summary · context
    We searched the PubMed, Cochrane, and Embase databases for RCTs of once-weekly tirzepatide vs. placebo or GLP-1 receptor agonists.
    Summary · context
    We included studies involving adult participants who were overweight or obese despite T2DM or OHA use, with a trial duration of at least 20 weeks.
    Summary · context
    We identified six RCTs in which the data of 6266 subjects were analysed.
  3. 03HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, a higher proportion of patients reached categorical weight loss goals with tirzepatide than in the comparator groups.

    In plain wordsIn adults with overweight or obesity, more people on tirzepatide reached the weight loss goals than in the comparator groups.

    Peptide
    Tirzepatide
    Outcome
    IncreaseProportion achieving categorical weight loss (5%, 10%, 15%)
    Study

    n = 6,266

    Comparator
    Placebo and GLP-1 receptor agonists
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    5, 10 and 15 mg once weekly · at least 20 weeksAs given in this study (human).

    Source sentences

    Summary
    Also, the proportion of patients achieving categorical weight loss goals was higher in the tirzepatide groups than in others.
    3 context sentences
    Summary · context
    We searched the PubMed, Cochrane, and Embase databases for RCTs of once-weekly tirzepatide vs. placebo or GLP-1 receptor agonists.
    Summary · context
    We included studies involving adult participants who were overweight or obese despite T2DM or OHA use, with a trial duration of at least 20 weeks.
    Summary · context
    We identified six RCTs in which the data of 6266 subjects were analysed.
  4. 04HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, GRADE assessment indicated high-certainty evidence for weight loss of 15% or more with tirzepatide.

    In plain wordsIn adults with overweight or obesity, there was high-certainty evidence that tirzepatide led to weight loss of 15% or more.

    Peptide
    Tirzepatide
    Outcome
    IncreaseWeight loss of 15% or more
    Study

    n = 6,266

    Comparator
    Placebo and GLP-1 receptor agonists
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    5, 10 and 15 mg once weekly · at least 20 weeksAs given in this study (human).

    Source sentences

    Summary
    GRADE assessment also indicated high-certainty evidence for ≥ 15% weight loss with tirzepatide and moderate-to-low certainty for lower thresholds.
    3 context sentences
    Summary · context
    We searched the PubMed, Cochrane, and Embase databases for RCTs of once-weekly tirzepatide vs. placebo or GLP-1 receptor agonists.
    Summary · context
    We included studies involving adult participants who were overweight or obese despite T2DM or OHA use, with a trial duration of at least 20 weeks.
    Summary · context
    We identified six RCTs in which the data of 6266 subjects were analysed.
  5. 05HumanSystematic reviewSafety outcome

    In adults with overweight or obesity, gastrointestinal side effects appeared similar between the three tirzepatide doses and GLP-1 receptor agonists.

    In plain wordsIn adults with overweight or obesity, stomach and gut side effects appeared similar for tirzepatide and other GLP-1 drugs.

    Peptide
    Tirzepatide
    Outcome
    No significant changeGastrointestinal side effects versus GLP-1 receptor agonists
    Study

    n: not reported in source

    Comparator
    GLP-1 receptor agonists
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    5, 10 and 15 mg once weekly · at least 20 weeksAs given in this study (human).

    Source sentences

    Summary
    Gastrointestinal side effects appeared similar between the three doses of tirzepatide and GLP-1 RAs
    3 context sentences
    Summary · context
    We searched the PubMed, Cochrane, and Embase databases for RCTs of once-weekly tirzepatide vs. placebo or GLP-1 receptor agonists.
    Summary · context
    We included studies involving adult participants who were overweight or obese despite T2DM or OHA use, with a trial duration of at least 20 weeks.
    Summary · context
    We identified six RCTs in which the data of 6266 subjects were analysed.
  6. 06HumanSystematic reviewSafety outcome

    In adults with overweight or obesity, gastrointestinal side effects with tirzepatide were significantly higher than with placebo.

    In plain wordsIn adults with overweight or obesity, stomach and gut side effects were significantly higher with tirzepatide than with placebo.

    Peptide
    Tirzepatide
    Outcome
    IncreaseGastrointestinal side effects versus placebo
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    5, 10 and 15 mg once weekly · at least 20 weeksAs given in this study (human).

    Source sentences

    Summary
    they were significantly higher than placebo might impact tolerability for certain patients.
    3 context sentences
    Summary · context
    We searched the PubMed, Cochrane, and Embase databases for RCTs of once-weekly tirzepatide vs. placebo or GLP-1 receptor agonists.
    Summary · context
    We included studies involving adult participants who were overweight or obese despite T2DM or OHA use, with a trial duration of at least 20 weeks.
    Summary · context
    We identified six RCTs in which the data of 6266 subjects were analysed.

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 · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT04255433

A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes

Eli Lilly and Companyn = 13,29929 May 2020 to 12 Jun 2025

Type 2 Diabetes Mellitus

Trial pageClinicalTrials.govUpdated 8 Jul 2026

Version history

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

  1. Versions 4 to 39Current

    28 Oct 2026, 02:04 UTC

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

    Study results updated

  2. Versions 2 to 3

    9 Oct 2026, 03:07 UTC

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

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:05 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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