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Study · Randomized controlled trial · 2025

3 results

Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency.

Bhatnagar P, Ahmad NN, Li X, Coghlan M, Kaplan LM, Farooqi IS

Nature medicine26 Aug 2025Cited by 15 (Europe PMC)

PMID40858971 (opens in a new tab)PMCIDPMC12532586 (opens in a new tab)DOI10.1038/s41591-025-03913-2 (opens in a new tab)PepBankPUB-40858971
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Summary

The magnitude of weight reduction in the SURMOUNT-1 trial of the dual GLP-1 and GIP receptor agonist tirzepatide suggests that this treatment may be particularly effective in addressing the treatment needs of people with severe obesity (body mass index >40 kg m-2), some of whom may carry rare penetrant genetic variants. Here we investigated the clinical response of men and women in the SURMOUNT-1 trial who carried pathogenic mutations in the melanocortin 4 receptor (MC4R) gene, the most common genetic cause of obesity. We found that 32 of 2,291 people (1.4%) for whom data were available carried pathogenic MC4R mutations. At baseline, MC4R mutation carriers exhibited a higher body mass index compared with noncarriers (40 kg m-2 versus 38 kg m-2; P = 0.036). In the treatment arm, the weight loss trajectory over 72 weeks was comparable in both groups: 18.3% weight reduction in MC4R mutation carriers versus 19.9% in noncarriers. We conclude that tirzepatide is an effective treatment for the most common genetic subtype of obesity, MC4R deficiency.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with obesity who carried pathogenic MC4R mutations in SURMOUNT-1, tirzepatide led to 18.3% weight reduction over 72 weeks.

    In plain wordsIn people with obesity caused by MC4R gene changes, tirzepatide led to 18.3% weight loss over 72 weeks.

    Peptide
    Tirzepatide
    Outcome
    DecreaseWeight reduction at 72 weeks in MC4R mutation carriers
    Study

    n: not reported in source

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 72 weeksAs given in this study (human).

    Measurements

    Weight reduction
    18.3%
    MC4R mutation carriers

    Source sentences

    Summary
    In the treatment arm, the weight loss trajectory over 72 weeks was comparable in both groups: 18.3% weight reduction in MC4R mutation carriers versus 19.9% in noncarriers.
    1 context sentence
    Summary · context
    Here we investigated the clinical response of men and women in the SURMOUNT-1 trial who carried pathogenic mutations in the melanocortin 4 receptor (MC4R) gene, the most common genetic cause of obesity.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In adults with obesity without pathogenic MC4R mutations in SURMOUNT-1, tirzepatide led to 19.9% weight reduction over 72 weeks.

    In plain wordsIn people with obesity without MC4R gene changes, tirzepatide led to 19.9% weight loss over 72 weeks.

    Peptide
    Tirzepatide
    Outcome
    DecreaseWeight reduction at 72 weeks in noncarriers
    Study

    n: not reported in source

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 72 weeksAs given in this study (human).

    Measurements

    Weight reduction
    19.9%
    MC4R noncarriers

    Source sentences

    Summary
    In the treatment arm, the weight loss trajectory over 72 weeks was comparable in both groups: 18.3% weight reduction in MC4R mutation carriers versus 19.9% in noncarriers.
    1 context sentence
    Summary · context
    Here we investigated the clinical response of men and women in the SURMOUNT-1 trial who carried pathogenic mutations in the melanocortin 4 receptor (MC4R) gene, the most common genetic cause of obesity.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In SURMOUNT-1, the weight loss trajectory with tirzepatide over 72 weeks was comparable in MC4R mutation carriers (18.3%) and noncarriers (19.9%).

    In plain wordsWith tirzepatide, weight loss over 72 weeks was similar in people with MC4R gene changes and in people without them.

    Peptide
    Tirzepatide
    Outcome
    No significant changeWeight loss in MC4R carriers versus noncarriers
    Study

    n: not reported in source

    Comparator
    Noncarriers of MC4R mutations
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 72 weeksAs given in this study (human).

    Measurements

    Weight reduction
    18.3%
    MC4R mutation carriers
    Weight reduction
    19.9%
    MC4R noncarriers

    Source sentences

    Summary
    In the treatment arm, the weight loss trajectory over 72 weeks was comparable in both groups: 18.3% weight reduction in MC4R mutation carriers versus 19.9% in noncarriers.
    1 context sentence
    Summary · context
    Here we investigated the clinical response of men and women in the SURMOUNT-1 trial who carried pathogenic mutations in the melanocortin 4 receptor (MC4R) gene, the most common genetic cause of obesity.

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 2Current

    12 Oct 2026, 12:58 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:07 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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