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Study · Observational study · n = 1,393 · 2026

8 results

Comparative effectiveness of tirzepatide and semaglutide for obesity management in US clinical practice: a 6-month retrospective cohort study.

le Roux CW, Done N, Brnabic AJM, Zion A, Lipkovich I, Kadziola Z, Dunn JP, Desai U, Kirson N, Dimitriadis GK, Kan H

Journal of endocrinological investigation9 Feb 2026Cited by 3 (Europe PMC)

PMID41661445 (opens in a new tab)PMCIDPMC12924827 (opens in a new tab)DOI10.1007/s40618-025-02792-1 (opens in a new tab)PepBankPUB-41661445
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Summary

PURPOSE: The SURMOUNT-5 trial demonstrated greater weight reduction with tirzepatide vs. semaglutide in adults with obesity without diabetes. This study compared real-world weight reduction and cardiometabolic parameters associated with tirzepatide and semaglutide for obesity management. METHODS: A retrospective cohort study was conducted using Truveta de-identified US electronic health record data. Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months. Primary outcome was percentage weight change from baseline. Secondary outcomes included weight-reduction targets and changes in body mass index (BMI) and cardiometabolic parameters. Primary analysis employed propensity-score weighted regression. Sensitivity analyses included modified intention-to-treat. RESULTS: Among 2,396 on-treatment patients (1,003 tirzepatide; 1,393 semaglutide), greater 6-month mean percentage weight reduction was observed with tirzepatide (–11.15% vs. −8.83%; adjusted difference −2.32%-points [95% CI: −3.17, −1.48]). Higher proportions of tirzepatide-treated patients achieved 5%, 10%, 15%, and 20% weight-reduction targets. Greater reductions in BMI, blood pressure, and haemoglobin A1c were observed with tirzepatide. More patients received higher doses of semaglutide (≥ 1.7 mg; 67.7%) vs. tirzepatide (≥ 10 mg; 42.4%). Sensitivity analysis findings were consistent. CONCLUSIONS: Consistent with clinical trials, real-world tirzepatide treatment was associated with greater 6-month weight reduction and more frequent achievement of weight-reduction targets and improvements in select cardiometabolic parameters than semaglutide among adults with obesity without diabetes. This early emergence of tirzepatide’s comparative advantage over semaglutide was observed despite more semaglutide-treated patients receiving higher doses than tirzepatide-treated patients.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

  1. 01HumanObservational studyEfficacy outcome

    In adults with obesity without diabetes, semaglutide gave a mean 6-month weight reduction of 8.83%, smaller than with tirzepatide.

    In plain wordsIn adults with obesity without diabetes, semaglutide led to a 6-month weight loss of 8.83%, less than with tirzepatide.

    Peptide
    Semaglutide
    Outcome
    DecreasePercentage weight change at 6 months
    Study

    n = 1,393

    Comparator
    Tirzepatide
    Analysis
    Primary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 6 monthsAs given in this study (human).

    Measurements

    Mean 6-month weight change
    −8.83%
    semaglutide

    Source sentences

    Summary
    Among 2,396 on-treatment patients (1,003 tirzepatide; 1,393 semaglutide), greater 6-month mean percentage weight reduction was observed with tirzepatide (–11.15% vs. −8.83%; adjusted difference −2.32%-points [95% CI: −3.17, −1.48]).
    2 context sentences
    Summary · context
    Primary outcome was percentage weight change from baseline.
    Summary · context
    Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months.
  2. 02HumanObservational studyEfficacy outcome

    In adults with obesity without diabetes, tirzepatide gave a greater 6-month weight reduction than semaglutide (adjusted difference -2.32 percentage points).

    In plain wordsIn adults with obesity without diabetes, tirzepatide led to more weight loss at 6 months than semaglutide in everyday care.

    Peptide
    Tirzepatide
    Outcome
    DecreasePercentage weight change at 6 months
    Study

    n = 1,003

    Comparator
    Semaglutide
    Analysis
    Primary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 6 monthsAs given in this study (human).

    Measurements

    Mean 6-month weight change
    −11.15%
    tirzepatide
    Adjusted difference versus semaglutide
    −2.32 %-points
    95% CI -3.17 to -1.48

    Source sentences

    Summary
    Among 2,396 on-treatment patients (1,003 tirzepatide; 1,393 semaglutide), greater 6-month mean percentage weight reduction was observed with tirzepatide (–11.15% vs. −8.83%; adjusted difference −2.32%-points [95% CI: −3.17, −1.48]).
    2 context sentences
    Summary · context
    Primary outcome was percentage weight change from baseline.
    Summary · context
    Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months.
  3. 03HumanObservational studyEfficacy outcome

    In adults with obesity without diabetes, higher proportions of tirzepatide-treated patients than semaglutide-treated patients reached 5%, 10%, 15% and 20% weight-reduction targets.

    In plain wordsIn adults with obesity without diabetes, more people on tirzepatide than on semaglutide reached each weight-loss target.

    Peptide
    Tirzepatide
    Outcome
    IncreaseProportion reaching 5%, 10%, 15% and 20% weight-reduction targets
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 6 monthsAs given in this study (human).

    Source sentences

    Summary
    Higher proportions of tirzepatide-treated patients achieved 5%, 10%, 15%, and 20% weight-reduction targets.
    1 context sentence
    Summary · context
    Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months.
  4. 04HumanObservational studyEfficacy outcome

    In adults with obesity without diabetes, tirzepatide reduced BMI more than semaglutide.

    In plain wordsIn adults with obesity without diabetes, tirzepatide lowered BMI more than semaglutide did.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBMI reduction
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 6 monthsAs given in this study (human).

    Source sentences

    Summary
    Greater reductions in BMI, blood pressure, and haemoglobin A1c were observed with tirzepatide.
    1 context sentence
    Summary · context
    Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months.
  5. 05HumanObservational studyEfficacy outcome

    In adults with obesity without diabetes, tirzepatide reduced blood pressure more than semaglutide.

    In plain wordsIn adults with obesity without diabetes, tirzepatide lowered blood pressure more than semaglutide did.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBlood pressure reduction
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Blood pressure · Cardiovascular
    Studied dose
    Dose not stated · 6 monthsAs given in this study (human).

    Source sentences

    Summary
    Greater reductions in BMI, blood pressure, and haemoglobin A1c were observed with tirzepatide.
    1 context sentence
    Summary · context
    Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months.
  6. 06HumanObservational studyEfficacy outcome

    In adults with obesity without diabetes, tirzepatide reduced haemoglobin A1c more than semaglutide.

    In plain wordsIn adults with obesity without diabetes, tirzepatide lowered haemoglobin A1c more than semaglutide did.

    Peptide
    Tirzepatide
    Outcome
    DecreaseHaemoglobin A1c reduction
    Study

    n: not reported in source

    Comparator
    Semaglutide
    Analysis
    Secondary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated · 6 monthsAs given in this study (human).

    Source sentences

    Summary
    Greater reductions in BMI, blood pressure, and haemoglobin A1c were observed with tirzepatide.
    1 context sentence
    Summary · context
    Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months.
  7. 07HumanObservational studyOther

    In adults with obesity without diabetes, 42.4% of tirzepatide-treated patients received a dose of 10 mg or more.

    In plain wordsIn adults with obesity without diabetes, 42.4% of people on tirzepatide received a dose of 10 mg or more.

    Peptide
    Tirzepatide
    Outcome
    Not applicableProportion on higher tirzepatide dose (10 mg or more)
    Study

    n: not reported in source

    Outcome group
    Patterns of use · Pharmacology
    Studied dose
    >=10 mg · 6 monthsAs given in this study (human).

    Measurements

    Patients on higher dose
    42.4%
    tirzepatide 10 mg or more

    Source sentences

    Summary
    More patients received higher doses of semaglutide (≥ 1.7 mg; 67.7%) vs. tirzepatide (≥ 10 mg; 42.4%).
    1 context sentence
    Summary · context
    Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months.
  8. 08HumanObservational studyOther

    In adults with obesity without diabetes, 67.7% of semaglutide-treated patients received a dose of 1.7 mg or more.

    In plain wordsIn adults with obesity without diabetes, 67.7% of people on semaglutide received a dose of 1.7 mg or more.

    Peptide
    Semaglutide
    Outcome
    Not applicableProportion on higher semaglutide dose (1.7 mg or more)
    Study

    n: not reported in source

    Outcome group
    Patterns of use · Pharmacology
    Studied dose
    >=1.7 mg · 6 monthsAs given in this study (human).

    Measurements

    Patients on higher dose
    67.7%
    semaglutide 1.7 mg or more

    Source sentences

    Summary
    More patients received higher doses of semaglutide (≥ 1.7 mg; 67.7%) vs. tirzepatide (≥ 10 mg; 42.4%).
    1 context sentence
    Summary · context
    Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months.

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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