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Study · Systematic review · 2026

6 results

Who Wins the Battle Against Obesity? A Network Meta-Analysis Comparing Tirzepatide and Semaglutide.

Bernardi JC, Cavalcante DVS, Huntermann R, Molinari ME, Zanon LZ, Khater J, Gomez VA, Fischer-Bacca CO

Journal of diabetes1 Feb 2026Cited by 6 (Europe PMC)

PMID41664890 (opens in a new tab)PMCIDPMC12887578 (opens in a new tab)DOI10.1111/1753-0407.70192 (opens in a new tab)PepBankPUB-41664890
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Summary

IntroductionPharmacological therapies are recommended for individuals with obesity. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1), and tirzepatide, a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist (GIP/GLP-1), are among the leading pharmacological options for obesity treatment. This network meta-analysis (NMA) aims to evaluate the comparative efficacy of these two agents in reducing body weight and improving glycemic parameters.MethodsPairwise comparisons within the NMA were conducted using a frequentist approach in RCTs comparing tirzepatide or semaglutide versus placebo, as well as tirzepatide versus semaglutide at their maximum dosages (15 and 2.4 mg, respectively).ResultsA total of 28 RCTs were included, comprising 34 367 participants, 39.6% of whom were women and with a mean age of 57.8 ± 8.95 years. Tirzepatide demonstrated superiority over semaglutide in percentage weight reduction (mean difference [MD] 6.10%; 95% CI: 3.64, 8.57), absolute weight loss (MD 4.55 kg; 95% CI: 1.28, 7.83), BMI reduction (MD 1.71 kg/m2; 95% CI: 0.08, 3.34), and waist circumference reduction (MD 2.89 cm; 95% CI: 1.25, 4.53). Regarding glycemic parameters, tirzepatide was also more effective than semaglutide in reducing HbA1c (MD 0.33%; 95% CI: 0.20, 0.46) and fasting blood glucose (MD 10.39 mg/dL; 95% CI: 4.48, 16.29).ConclusionIn this NMA, tirzepatide appeared to be superior to semaglutide in both body weight reduction and improvement of glycemic indices.
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 obesity, network meta-analysis of RCTs found tirzepatide 15 mg reduced body weight percentage more than semaglutide 2.4 mg (mean difference 6.10%).

    In plain wordsIn adults with obesity, tirzepatide led to more percentage weight loss than semaglutide in a pooled analysis of trials.

    Peptide
    Tirzepatide
    Outcome
    DecreasePercentage weight reduction
    Study

    n: not reported in source

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

    Measurements

    Mean difference
    6.1%
    tirzepatide versus semaglutide

    Source sentences

    Summary
    percentage weight reduction (mean difference [MD] 6.10%; 95% CI: 3.64, 8.57)
    2 context sentences
    Summary · context
    Pairwise comparisons within the NMA were conducted using a frequentist approach in RCTs comparing tirzepatide or semaglutide versus placebo, as well as tirzepatide versus semaglutide at their maximum dosages (15 and 2.4 mg, respectively).
    Summary · context
    A total of 28 RCTs were included, comprising 34 367 participants, 39.6% of whom were women and with a mean age of 57.8 ± 8.95 years.
  2. 02HumanSystematic reviewEfficacy outcome

    In adults with obesity, network meta-analysis of RCTs found tirzepatide 15 mg produced greater absolute weight loss than semaglutide 2.4 mg (mean difference 4.55 kg).

    In plain wordsIn adults with obesity, tirzepatide led to more kilograms of weight loss than semaglutide in a pooled analysis of trials.

    Peptide
    Tirzepatide
    Outcome
    DecreaseAbsolute weight loss
    Study

    n: not reported in source

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

    Measurements

    Mean difference
    4.55 kg
    tirzepatide versus semaglutide

    Source sentences

    Summary
    absolute weight loss (MD 4.55 kg; 95% CI: 1.28, 7.83)
    2 context sentences
    Summary · context
    Pairwise comparisons within the NMA were conducted using a frequentist approach in RCTs comparing tirzepatide or semaglutide versus placebo, as well as tirzepatide versus semaglutide at their maximum dosages (15 and 2.4 mg, respectively).
    Summary · context
    A total of 28 RCTs were included, comprising 34 367 participants, 39.6% of whom were women and with a mean age of 57.8 ± 8.95 years.
  3. 03HumanSystematic reviewEfficacy outcome

    In adults with obesity, network meta-analysis of RCTs found tirzepatide 15 mg reduced BMI more than semaglutide 2.4 mg (mean difference 1.71 kg/m2).

    In plain wordsIn adults with obesity, tirzepatide lowered BMI more than semaglutide in a pooled analysis of trials.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBMI reduction
    Study

    n: not reported in source

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

    Measurements

    Mean difference
    1.71 kg/m2
    tirzepatide versus semaglutide

    Source sentences

    Summary
    BMI reduction (MD 1.71 kg/m2; 95% CI: 0.08, 3.34)
    2 context sentences
    Summary · context
    Pairwise comparisons within the NMA were conducted using a frequentist approach in RCTs comparing tirzepatide or semaglutide versus placebo, as well as tirzepatide versus semaglutide at their maximum dosages (15 and 2.4 mg, respectively).
    Summary · context
    A total of 28 RCTs were included, comprising 34 367 participants, 39.6% of whom were women and with a mean age of 57.8 ± 8.95 years.
  4. 04HumanSystematic reviewEfficacy outcome

    In adults with obesity, network meta-analysis of RCTs found tirzepatide 15 mg reduced waist circumference more than semaglutide 2.4 mg (mean difference 2.89 cm).

    In plain wordsIn adults with obesity, tirzepatide shrank waist size more than semaglutide in a pooled analysis of trials.

    Peptide
    Tirzepatide
    Outcome
    DecreaseWaist circumference reduction
    Study

    n: not reported in source

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

    Measurements

    Mean difference
    2.89 cm
    tirzepatide versus semaglutide

    Source sentences

    Summary
    waist circumference reduction (MD 2.89 cm; 95% CI: 1.25, 4.53)
    2 context sentences
    Summary · context
    Pairwise comparisons within the NMA were conducted using a frequentist approach in RCTs comparing tirzepatide or semaglutide versus placebo, as well as tirzepatide versus semaglutide at their maximum dosages (15 and 2.4 mg, respectively).
    Summary · context
    A total of 28 RCTs were included, comprising 34 367 participants, 39.6% of whom were women and with a mean age of 57.8 ± 8.95 years.
  5. 05HumanSystematic reviewEfficacy outcome

    In network meta-analysis of RCTs, tirzepatide 15 mg reduced HbA1c more than semaglutide 2.4 mg (mean difference 0.33%).

    In plain wordsIn a pooled analysis of trials, tirzepatide lowered HbA1c more than semaglutide.

    Peptide
    Tirzepatide
    Outcome
    DecreaseHbA1c reduction
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    15 mgAs given in this study (human).

    Measurements

    Mean difference
    0.33%
    tirzepatide versus semaglutide

    Source sentences

    Summary
    reducing HbA1c (MD 0.33%; 95% CI: 0.20, 0.46)
    2 context sentences
    Summary · context
    Pairwise comparisons within the NMA were conducted using a frequentist approach in RCTs comparing tirzepatide or semaglutide versus placebo, as well as tirzepatide versus semaglutide at their maximum dosages (15 and 2.4 mg, respectively).
    Summary · context
    A total of 28 RCTs were included, comprising 34 367 participants, 39.6% of whom were women and with a mean age of 57.8 ± 8.95 years.
  6. 06HumanSystematic reviewEfficacy outcome

    In network meta-analysis of RCTs, tirzepatide 15 mg reduced fasting blood glucose more than semaglutide 2.4 mg (mean difference 10.39 mg/dL).

    In plain wordsIn a pooled analysis of trials, tirzepatide lowered fasting blood glucose more than semaglutide.

    Peptide
    Tirzepatide
    Outcome
    DecreaseFasting blood glucose reduction
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    15 mgAs given in this study (human).

    Measurements

    Mean difference
    10.39 mg/dL
    tirzepatide versus semaglutide

    Source sentences

    Summary
    fasting blood glucose (MD 10.39 mg/dL; 95% CI: 4.48, 16.29)
    2 context sentences
    Summary · context
    Pairwise comparisons within the NMA were conducted using a frequentist approach in RCTs comparing tirzepatide or semaglutide versus placebo, as well as tirzepatide versus semaglutide at their maximum dosages (15 and 2.4 mg, respectively).
    Summary · context
    A total of 28 RCTs were included, comprising 34 367 participants, 39.6% of whom were women and with a mean age of 57.8 ± 8.95 years.

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 3Current

    11 Oct 2026, 00:04 UTC

    Study results updated

  2. Version 2

    9 Oct 2026, 03:07 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:06 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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