Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial.

Martin CK, Carmichael OT, Carnell S, Considine RV, Kareken DA, Dydak U, Mattes RD, Scott D, Shcherbinin S, Nishiyama H, Knights A, Urva S and 7 more

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Biernat L, Pratt E, Haupt A, Mintun M, Otero Svaldi D, Milicevic Z, Coskun T

Nature medicine24 Jun 2025Cited by 52 (Europe PMC)

PMID40555748PMCIDPMC12443625DOI10.1038/s41591-025-03774-9PepBankPUB-40555748

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Summary

Tirzepatide induces weight reduction but the underlying mechanisms are unknown. This 6-week phase 1 study investigated early effects of tirzepatide on energy intake. Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide. The primary outcome was change from baseline to week 3 in energy intake during an ad libitum lunch with tirzepatide versus placebo. Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos. Tirzepatide reduced energy intake versus placebo at week 3 (estimated treatment difference -524.6 kcal (95% confidence interval -648.1 to -401.0), P < 0.0001). With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake. At week 3 versus placebo, tirzepatide did not statistically significantly impact blood-oxygenation-level-dependent activation to highly palatable food photos (aggregated category of high-fat, high-sugar foods and high-fat, high-carbohydrate foods) but decreased activation to high-fat, high-sugar food photos in the medial frontal and cingulate gyri, orbitofrontal cortex and hippocampus. Our results suggest tirzepatide reduces food intake, potentially by impacting ingestive behavior. ClinicalTrials.gov registration: NCT04311411 .

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

12 results from studies that gave the peptide. 12 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide reduced energy intake versus placebo at week 3 (estimated treatment difference -524.6 kcal; 95% CI -648.1 to -401.0; P < 0.0001).
In plain wordsIn adults without diabetes with BMI 27-50, tirzepatide reduced food energy intake more than placebo at week 3.
Peptide
Tirzepatide
Outcome
DecreaseEnergy intake at week 3
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Measurements
Estimated treatment difference
−524.6 kcal
tirzepatide versus placebo at week 3
95% CI
−648.1 to −401 kcal
week 3 difference
P-value
< 0.0001
primary energy-intake contrast
Source sentences
Summary
Tirzepatide reduced energy intake versus placebo at week 3 (estimated treatment difference -524.6 kcal (95% confidence interval -648.1 to -401.0), P < 0.0001).
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
The primary outcome was change from baseline to week 3 in energy intake during an ad libitum lunch with tirzepatide versus placebo.
Show in the study text Report a problemFND-4055574801
02HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide decreased overall appetite versus placebo.
In plain wordsIn adults without diabetes with BMI 27-50, tirzepatide lowered appetite more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseOverall appetite
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574802
03HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide decreased food cravings versus placebo.
In plain wordsIn adults without diabetes with BMI 27-50, tirzepatide lowered food cravings more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseFood cravings
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574803
04HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide decreased tendency to overeat versus placebo.
In plain wordsIn adults without diabetes with BMI 27-50, tirzepatide lowered tendency to overeat more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseTendency to overeat
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574804
05HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide decreased perceived hunger versus placebo.
In plain wordsIn adults without diabetes with BMI 27-50, tirzepatide lowered perceived hunger more than placebo.
Peptide
Tirzepatide
Outcome
DecreasePerceived hunger
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574805
06HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide decreased food-environment reactivity versus placebo.
In plain wordsIn adults without diabetes with BMI 27-50, tirzepatide lowered food-environment reactivity more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseFood-environment reactivity
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574806
07HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with overweight or obesity, tirzepatide reportedly did not affect voluntary dietary restriction versus placebo; no endpoint-specific significance test was stated.
In plain wordsIn adults without diabetes with overweight or obesity, tirzepatide reportedly did not affect voluntary dietary restriction versus placebo; the test was unstated.
Peptide
Tirzepatide
Outcome
Direction not reportedVolitional dietary restriction
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574807
08HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide did not significantly impact BOLD activation to highly palatable food photos versus placebo at week 3.
In plain wordsIn adults without diabetes with overweight or obesity, tirzepatide showed no significant brain activation difference for highly palatable images versus placebo at week 3.
Peptide
Tirzepatide
Outcome
No significant changeBOLD activation to highly palatable food photos
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
At week 3 versus placebo, tirzepatide did not statistically significantly impact blood-oxygenation-level-dependent activation to highly palatable food photos (aggregated category of high-fat, high-sugar foods and high-fat, high-carbohydrate foods) but decreased activation to high-fat, high-sugar food photos in the medial frontal and cingulate gyri, orbitofrontal cortex and hippocampus.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574808
09HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide decreased activation to high-fat, high-sugar food photos in the medial frontal gyrus versus placebo at week 3.
In plain wordsIn adults without diabetes with overweight or obesity, tirzepatide reduced medial frontal activation to high-fat, high-sugar images versus placebo at week 3.
Peptide
Tirzepatide
Outcome
DecreaseBOLD activation to high-fat, high-sugar food photos in medial frontal gyrus
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
At week 3 versus placebo, tirzepatide did not statistically significantly impact blood-oxygenation-level-dependent activation to highly palatable food photos (aggregated category of high-fat, high-sugar foods and high-fat, high-carbohydrate foods) but decreased activation to high-fat, high-sugar food photos in the medial frontal and cingulate gyri, orbitofrontal cortex and hippocampus.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574809
10HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide decreased activation to high-fat, high-sugar food photos in the cingulate gyri versus placebo at week 3.
In plain wordsIn adults without diabetes with overweight or obesity, tirzepatide reduced cingulate activation to high-fat, high-sugar images versus placebo at week 3.
Peptide
Tirzepatide
Outcome
DecreaseBOLD activation to high-fat, high-sugar food photos in cingulate gyri
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
At week 3 versus placebo, tirzepatide did not statistically significantly impact blood-oxygenation-level-dependent activation to highly palatable food photos (aggregated category of high-fat, high-sugar foods and high-fat, high-carbohydrate foods) but decreased activation to high-fat, high-sugar food photos in the medial frontal and cingulate gyri, orbitofrontal cortex and hippocampus.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574810
11HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide decreased activation to high-fat, high-sugar food photos in the orbitofrontal cortex versus placebo at week 3.
In plain wordsIn adults without diabetes with overweight or obesity, tirzepatide reduced orbitofrontal activation to high-fat, high-sugar images versus placebo at week 3.
Peptide
Tirzepatide
Outcome
DecreaseBOLD activation to high-fat, high-sugar food photos in orbitofrontal cortex
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
At week 3 versus placebo, tirzepatide did not statistically significantly impact blood-oxygenation-level-dependent activation to highly palatable food photos (aggregated category of high-fat, high-sugar foods and high-fat, high-carbohydrate foods) but decreased activation to high-fat, high-sugar food photos in the medial frontal and cingulate gyri, orbitofrontal cortex and hippocampus.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574811
12HumanRandomized controlled trialEfficacy outcome
In adults without diabetes with BMI 27-50 kg/m², tirzepatide decreased activation to high-fat, high-sugar food photos in the hippocampus versus placebo at week 3.
In plain wordsIn adults without diabetes with overweight or obesity, tirzepatide reduced hippocampal activation to high-fat, high-sugar images versus placebo at week 3.
Peptide
Tirzepatide
Outcome
DecreaseBOLD activation to high-fat, high-sugar food photos in hippocampus
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
At week 3 versus placebo, tirzepatide did not statistically significantly impact blood-oxygenation-level-dependent activation to highly palatable food photos (aggregated category of high-fat, high-sugar foods and high-fat, high-carbohydrate foods) but decreased activation to high-fat, high-sugar food photos in the medial frontal and cingulate gyri, orbitofrontal cortex and hippocampus.
2 context sentences(design, population, supporting numbers)
Summary · context
Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m² were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide.
Summary · context
Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos.
Show in the study text Report a problemFND-4055574812

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 1Results postedNCT04311411

A Study of Tirzepatide in Overweight and Very Overweight Participants

Eli Lilly and Companyn = 11424 Aug 2020 to 16 Dec 2022

Obesity · Overweight

Trial page ClinicalTrials.govUpdated 22 May 2024

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.

Version 3Current
12 Oct 2026, 11:11 UTC
Study results updated
Version 2
9 Oct 2026, 03:07 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC