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Study · Case report or series · n = 1 · 2026

5 results

Tirzepatide non-response with subsequent semaglutide response in class 2 obesity.

La Vignera S, Condorelli RA

JCEM case reports31 Aug 2026

PMID42670558 (opens in a new tab)PMCIDPMC13526503 (opens in a new tab)DOI10.1210/jcemcr/luag245 (opens in a new tab)PepBankPUB-42670558
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Summary

We report a paradoxical case of a 40-year-old man with class 2 obesity (body mass index 39.8 kg/m2) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] 5.0; reference <2.0) who achieved minimal weight loss (<5%) despite tirzepatide dose escalation to 15 mg weekly over 6 months. Following switch to semaglutide 2.4 mg weekly, the patient achieved 20% weight loss over 6 months, with normalization of fasting glucose, resolution of insulin resistance, and marked improvement in appetite control. This case challenges the assumption that dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonism is universally superior to selective GLP-1 receptor agonism for weight management. Mechanistic analysis suggests that adipose tissue GIP receptor downregulation in the context of class 2 obesity and insulin resistance, combined with intact central GLP-1 receptor signaling, may explain the differential response in some individuals. Key learning points include: markedly elevated baseline insulin resistance (HOMA-IR ≥4-5) may be associated with poor tirzepatide response, though prospective validation is required; persistent hyperphagia during tirzepatide treatment is an early warning sign; and nonresponse to tirzepatide does not preclude semaglutide response. This case supports precision medicine approaches in obesity pharmacotherapy, including pretreatment phenotyping and early response assessment.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

1 result from studies that gave the peptide. 1 result from people.

  1. 01HumanCase report or seriesEfficacy outcome

    In a man with class 2 obesity and insulin resistance, tirzepatide escalated to 15 mg weekly over 6 months produced minimal weight loss (under 5%).

    In plain wordsIn one man with obesity, tirzepatide at 15 mg weekly for 6 months led to very little weight loss.

    Peptide
    Tirzepatide
    Outcome
    No significant changeWeight loss on tirzepatide
    Study

    n = 1

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    15 mg weekly · 6 monthsAs given in this study (human).

    Measurements

    Weight loss
    < 5%
    tirzepatide 15 mg weekly

    Source sentences

    Summary
    who achieved minimal weight loss (<5%) despite tirzepatide dose escalation to 15 mg weekly over 6 months.
    1 context sentence
    Summary · context
    We report a paradoxical case of a 40-year-old man with class 2 obesity (body mass index 39.8 kg/m2) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] 5.0; reference <2.0) who achieved minimal weight loss (<5%) despite tirzepatide dose escalation to 15 mg weekly over 6 months.

Studies that did not test the peptide alone4

In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Semaglutide.

  1. 02HumanNot a test of Semaglutide aloneCase report or seriesEfficacy outcome

    In a man with class 2 obesity who did not respond to tirzepatide, switching to semaglutide 2.4 mg weekly led to 20% weight loss over 6 months.

    In plain wordsIn one man with obesity who lost little weight on tirzepatide, switching to semaglutide led to 20% weight loss over 6 months.

    Peptide
    Semaglutide
    Outcome
    DecreaseWeight loss after switch to semaglutide
    Study

    n = 1

    Outcome group
    Body weight · Metabolic and weight

    Measurements

    Weight loss
    20%
    semaglutide 2.4 mg weekly

    Source sentences

    Summary
    Following switch to semaglutide 2.4 mg weekly, the patient achieved 20% weight loss over 6 months
    1 context sentence
    Summary · context
    We report a paradoxical case of a 40-year-old man with class 2 obesity (body mass index 39.8 kg/m2) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] 5.0; reference <2.0) who achieved minimal weight loss (<5%) despite tirzepatide dose escalation to 15 mg weekly over 6 months.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  2. 03HumanNot a test of Semaglutide aloneCase report or seriesEfficacy outcome

    In a man with class 2 obesity, fasting glucose normalized after switching from tirzepatide to semaglutide.

    In plain wordsIn one man with obesity, fasting blood sugar returned to normal after switching from tirzepatide to semaglutide.

    Peptide
    Semaglutide
    Outcome
    DecreaseFasting glucose after switch to semaglutide
    Study

    n = 1

    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    with normalization of fasting glucose
    1 context sentence
    Summary · context
    We report a paradoxical case of a 40-year-old man with class 2 obesity (body mass index 39.8 kg/m2) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] 5.0; reference <2.0) who achieved minimal weight loss (<5%) despite tirzepatide dose escalation to 15 mg weekly over 6 months.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  3. 04HumanNot a test of Semaglutide aloneCase report or seriesEfficacy outcome

    In a man with class 2 obesity, insulin resistance resolved after switching from tirzepatide to semaglutide.

    In plain wordsIn one man with obesity, insulin resistance went away after switching from tirzepatide to semaglutide.

    Peptide
    Semaglutide
    Outcome
    DecreaseInsulin resistance after switch to semaglutide
    Study

    n = 1

    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    resolution of insulin resistance, and marked improvement in appetite control.
    1 context sentence
    Summary · context
    We report a paradoxical case of a 40-year-old man with class 2 obesity (body mass index 39.8 kg/m2) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] 5.0; reference <2.0) who achieved minimal weight loss (<5%) despite tirzepatide dose escalation to 15 mg weekly over 6 months.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  4. 05HumanNot a test of Semaglutide aloneCase report or seriesEfficacy outcome

    In a man with class 2 obesity, appetite control improved markedly after switching from tirzepatide to semaglutide.

    In plain wordsIn one man with obesity, appetite control improved a lot after switching from tirzepatide to semaglutide.

    Peptide
    Semaglutide
    Outcome
    IncreaseAppetite control after switch to semaglutide
    Study

    n = 1

    Outcome group
    Appetite and food intake · Metabolic and weight

    Source sentences

    Summary
    marked improvement in appetite control.
    1 context sentence
    Summary · context
    We report a paradoxical case of a 40-year-old man with class 2 obesity (body mass index 39.8 kg/m2) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] 5.0; reference <2.0) who achieved minimal weight loss (<5%) despite tirzepatide dose escalation to 15 mg weekly over 6 months.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

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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