Skip to content

Study · Systematic review · n = 41,381 · 2026

13 results

Comparative Efficacy of Tirzepatide Versus Semaglutide for Weight Loss in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Head-to-Head Studies.

Paccola GP, de Oliveira RF, Mochetti MM, Razera FPM, Vecchi R, Montanher RCP

Clinical obesity1 Oct 2026

PMID42670242 (opens in a new tab)PMCIDPMC13527552 (opens in a new tab)DOI10.1111/cob.70111 (opens in a new tab)PepBankPUB-42670242
Download PDFPubMedAsk about this study
Jump to 13 results

Summary

This systematic review and meta-analysis aimed to compare the efficacy and safety of tirzepatide versus semaglutide for weight reduction in adults with overweight or obesity. We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up. The primary outcome was percentage weight change from baseline. Secondary outcomes included absolute weight change, weight-loss thresholds, HbA1c and safety outcomes. Ten studies including 41 381 participants were analysed. Tirzepatide was associated with greater percentage weight reduction than semaglutide (MD -4.28 percentage points; 95% CI -5.28 to -3.28; p < 0.00001) and greater absolute weight loss (MD -4.43 kg; 95% CI -5.56 to -3.30; p < 0.00001). Tirzepatide was also associated with a higher likelihood of achieving ≥ 10%, ≥ 15% and ≥ 20% weight loss, with no difference at ≥ 5%. HbA1c reduction was greater with tirzepatide (MD -0.29%; p = 0.0002). Subgroup analyses by study design and type 2 diabetes status yielded consistent findings. There was no significant difference in treatment discontinuation due to adverse events (RR 1.28; p = 0.54), whereas serious adverse events were more frequent with tirzepatide (RR 1.83; p = 0.007). Overall and gastrointestinal adverse events were similar between groups. Tirzepatide was associated with greater weight reduction, greater glycaemic benefit and a higher likelihood of achieving weight-loss thresholds than semaglutide, but with a higher risk of serious adverse events.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study13

13 results from studies that gave the peptide. 13 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, tirzepatide was associated with greater percentage weight reduction than semaglutide in a meta-analysis of head-to-head studies.

    In plain wordsIn adults with overweight or obesity, tirzepatide was linked to more weight loss than semaglutide.

    Peptide
    Tirzepatide
    Outcome
    DecreasePercentage weight change
    Study

    n = 41,381

    Comparator
    Semaglutide
    Analysis
    Primary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Mean difference in weight change
    −4.28 percentage points
    tirzepatide vs semaglutide

    Source sentences

    Summary
    Tirzepatide was associated with greater percentage weight reduction than semaglutide (MD -4.28 percentage points; 95% CI -5.28 to -3.28; p < 0.00001)
    2 context sentences
    Summary · context
    Ten studies including 41 381 participants were analysed.
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  2. 02HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, semaglutide was associated with smaller percentage weight reduction than tirzepatide in a meta-analysis of head-to-head studies.

    In plain wordsIn adults with overweight or obesity, semaglutide was linked to less weight loss than tirzepatide.

    Peptide
    Semaglutide
    Outcome
    IncreasePercentage weight change relative to tirzepatide
    Study

    n: not reported in source

    Comparator
    Tirzepatide
    Analysis
    Primary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Mean difference in weight change
    −4.28 percentage points
    tirzepatide vs semaglutide

    Source sentences

    Summary
    Tirzepatide was associated with greater percentage weight reduction than semaglutide (MD -4.28 percentage points; 95% CI -5.28 to -3.28; p < 0.00001)
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  3. 03HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, tirzepatide was associated with greater absolute weight loss than semaglutide.

    In plain wordsIn adults with overweight or obesity, tirzepatide was linked to more kilograms lost than semaglutide.

    Peptide
    Tirzepatide
    Outcome
    DecreaseAbsolute weight change
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Mean difference in absolute weight change
    −4.43 kg
    tirzepatide vs semaglutide

    Source sentences

    Summary
    and greater absolute weight loss (MD -4.43 kg; 95% CI -5.56 to -3.30; p < 0.00001).
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  4. 04HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, tirzepatide was associated with a higher likelihood than semaglutide of achieving at least 10% weight loss.

    In plain wordsIn adults with overweight or obesity, tirzepatide was linked to a higher chance of losing at least 10% of body weight than semaglutide.

    Peptide
    Tirzepatide
    Outcome
    IncreaseAchieving 10% or more weight loss
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Tirzepatide was also associated with a higher likelihood of achieving ≥ 10%, ≥ 15% and ≥ 20% weight loss, with no difference at ≥ 5%.
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  5. 05HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, tirzepatide was associated with a higher likelihood than semaglutide of achieving at least 15% weight loss.

    In plain wordsIn adults with overweight or obesity, tirzepatide was linked to a higher chance of losing at least 15% of body weight than semaglutide.

    Peptide
    Tirzepatide
    Outcome
    IncreaseAchieving 15% or more weight loss
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Tirzepatide was also associated with a higher likelihood of achieving ≥ 10%, ≥ 15% and ≥ 20% weight loss, with no difference at ≥ 5%.
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  6. 06HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, tirzepatide was associated with a higher likelihood than semaglutide of achieving at least 20% weight loss.

    In plain wordsIn adults with overweight or obesity, tirzepatide was linked to a higher chance of losing at least 20% of body weight than semaglutide.

    Peptide
    Tirzepatide
    Outcome
    IncreaseAchieving 20% or more weight loss
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Tirzepatide was also associated with a higher likelihood of achieving ≥ 10%, ≥ 15% and ≥ 20% weight loss, with no difference at ≥ 5%.
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  7. 07HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, there was no difference between tirzepatide and semaglutide in the likelihood of achieving at least 5% weight loss.

    In plain wordsIn adults with overweight or obesity, tirzepatide and semaglutide gave a similar chance of losing at least 5% of body weight.

    Peptide
    Tirzepatide
    Outcome
    No significant changeAchieving 5% or more weight loss
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Tirzepatide was also associated with a higher likelihood of achieving ≥ 10%, ≥ 15% and ≥ 20% weight loss, with no difference at ≥ 5%.
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  8. 08HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, HbA1c reduction was greater with tirzepatide than with semaglutide.

    In plain wordsIn adults with overweight or obesity, tirzepatide lowered HbA1c more than semaglutide.

    Peptide
    Tirzepatide
    Outcome
    DecreaseHbA1c reduction
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Mean difference in HbA1c
    −0.29%
    tirzepatide vs semaglutide

    Source sentences

    Summary
    HbA1c reduction was greater with tirzepatide (MD -0.29%; p = 0.0002).
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  9. 09HumanSystematic reviewSafety outcome

    There was no significant difference between tirzepatide and semaglutide in treatment discontinuation due to adverse events.

    In plain wordsTirzepatide and semaglutide did not differ significantly in how many people stopped treatment because of side effects.

    Peptide
    Tirzepatide
    Outcome
    No significant changeDiscontinuation due to adverse events
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Measurements

    RR
    1.28 ratio
    discontinuation due to adverse events

    Source sentences

    Summary
    There was no significant difference in treatment discontinuation due to adverse events (RR 1.28; p = 0.54)
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  10. 10HumanSystematic reviewSafety outcome

    Serious adverse events were more frequent with tirzepatide than with semaglutide.

    In plain wordsTirzepatide was linked to more serious side effects than semaglutide.

    Peptide
    Tirzepatide
    Outcome
    IncreaseSerious adverse events
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Measurements

    RR
    1.83 ratio
    serious adverse events

    Source sentences

    Summary
    whereas serious adverse events were more frequent with tirzepatide (RR 1.83; p = 0.007).
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  11. 11HumanSystematic reviewSafety outcome

    Overall adverse events were similar between tirzepatide and semaglutide.

    In plain wordsTirzepatide and semaglutide caused a similar number of side effects overall.

    Peptide
    Tirzepatide
    Outcome
    No significant changeOverall adverse events
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Overall and gastrointestinal adverse events were similar between groups.
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  12. 12HumanSystematic reviewSafety outcome

    Gastrointestinal adverse events were similar between tirzepatide and semaglutide.

    In plain wordsTirzepatide and semaglutide caused a similar number of stomach and gut side effects.

    Peptide
    Tirzepatide
    Outcome
    No significant changeGastrointestinal adverse events
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Overall and gastrointestinal adverse events were similar between groups.
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.
  13. 13HumanSystematic reviewSafety outcome

    Serious adverse events were less frequent with semaglutide than with tirzepatide.

    In plain wordsSemaglutide was linked to fewer serious side effects than tirzepatide.

    Peptide
    Semaglutide
    Outcome
    DecreaseSerious adverse events relative to tirzepatide
    Study

    n: not reported in source

    Comparator
    Tirzepatide
    Analysis
    Secondary
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    whereas serious adverse events were more frequent with tirzepatide (RR 1.83; p = 0.007).
    1 context sentence
    Summary · context
    We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up.

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.

PepBank is a research reference. Talk to a doctor before you use any peptide.