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References support the discussion topics. They do not mean the wording of the questions has been clinically validated.

NUVITEO · Discussion guide

Questions for Your Visit

Choose at least one question on the Questions for Your Visit page before printing your personal question sheet.

These questions are prompts for a conversation about your care.

References support the discussion topics. They do not mean the wording of the questions has been clinically validated.

OVERVIEW + STUDY DETAILS

References behind the discussion topics.

Start with the finding and its limits.
Open the study details to look closer.

Conceptual consensus

EWGSOP2: sarcopenia definition and assessment

In this analysis, DXA lean mass is fat-free mass minus bone mineral content. It includes tissues other than muscle and, alone, does not describe strength or diagnose sarcopenia.

Under EWGSOP2, low strength indicates probable sarcopenia; low muscle quantity or quality confirms the diagnosis, and low physical performance together with the other criteria identifies severe sarcopenia.

Evidence design
Diagnostic consensus concept

Keep in view

  • Diagnostic consensus; it does not estimate a treatment effect or individual risk.
  • A decrease in total DXA lean mass alone does not diagnose sarcopenia.
See study details — EWGSOP2

Definitions and assessment framework

Diagnostic consensus concept

Expert consensus updating the European definition and diagnostic approach to sarcopenia; not an intervention trial.

Diagnostic concepts
  • Diagnostic state
    Probable sarcopenia
    Definition
    Low muscle strength identifies probable sarcopenia.
  • Diagnostic state
    Confirmed sarcopenia
    Definition
    Low muscle quantity or quality confirms the diagnosis in the presence of low strength.
  • Diagnostic state
    Severe sarcopenia
    Definition
    Low strength, low muscle quantity/quality and low physical performance together identify severe sarcopenia.
Assessment sequence
  • Find cases
  • Assess muscle strength
  • Confirm muscle quantity or quality
  • Determine severity with physical performance

What the curated evidence supports

  • In this analysis, DXA lean mass is fat-free mass minus bone mineral content. It includes tissues other than muscle and, alone, does not describe strength or diagnose sarcopenia.
  • Under EWGSOP2, low strength indicates probable sarcopenia; low muscle quantity or quality confirms the diagnosis, and low physical performance together with the other criteria identifies severe sarcopenia.

Limitations

  • Diagnostic consensus; it does not estimate a treatment effect or individual risk.
  • A decrease in total DXA lean mass alone does not diagnose sarcopenia.

Verification scope

Verified through 2026-11-04 within the consulted scope.

Bibliographic metadata checked
Yes
Original article abstract consulted
Yes
Full-text consultation
Consulted
Official trial registry consulted
No
Statistical analysis plan consulted
No
Verification boundary
Verification is limited to the specific fields and sources consulted; it is not a full systematic appraisal or GRADE rating.

Source record

Sarcopenia: revised European consensus on definition and diagnosis (2019). Age and ageing.

Source identifiers

  • Article DOI: 10.1093/ageing/afy169
  • PubMed record 30312372
  • PubMed Central: PMC6322506

Controlled study

Short sleep, hormones and hunger: the Spiegel experiment

In a crossover experiment involving 12 young men, restricted sleep was associated with 18% lower leptin, 28% higher ghrelin and 24% greater subjective hunger than sleep extension.

Evidence design
Randomized crossover clinical trial
Population
Healthy young men; mean age 22 years and mean BMI 23.6 kg/m².
Assessment period
After two days in each experimental condition
Reported units
% relative difference

Keep in view

  • Only 12 young men, with two two-day conditions; not representative of all populations.
  • It does not establish future weight gain or a universal hormonal pattern.
See study details — Sleep restriction experiment

Study design and methods

Randomized crossover clinical trial

Randomized crossover trial with two two-day conditions; caloric intake and activity were controlled.

Population

Healthy young men; mean age 22 years and mean BMI 23.6 kg/m².

Study design
Randomized crossover trial with two two-day conditions; caloric intake and activity were controlled.
Reported sample count
12
Role of the reported sample count
Reported study sample; not necessarily the denominator for each outcome
Included study count
1
Role of the study count
Single study
Research question
Does partial sleep restriction alter appetite-related hormones and perceived hunger?
Qualified findings
In this small experiment, the restricted-sleep period showed lower leptin, higher ghrelin and greater hunger/appetite than the sleep-extension period. The finding provides short-term experimental evidence without establishing a universal hormonal pattern.
Estimand and analysis rules
Not reported or not verified
Reason the formal estimand is unavailable
A complete formal estimand was not extracted from the verified input.

Extracted outcomes

Reported values, analysis populations and uncertainty, preserved from the curated extraction.
Outcome and groupReported valueAssessment periodSample and denominatorsUncertainty
Mean leptin

Sleep restriction versus extension

Effect estimate

-18 % relative difference

reported relative difference

Unit: % relative difference

After two days in each experimental condition

Reported N: 12 — unique crossover-study participants; not an outcome-specific denominator

  • 12 — unique participants; scope: crossover study

CI not supplied in the verified scope.

Reported p-value: 0.04 (between condition comparison)

Mean ghrelin

Sleep restriction versus extension

Effect estimate

28 % relative difference

reported relative difference

Unit: % relative difference

After two days in each experimental condition

Reported N: 12 — unique crossover-study participants; not an outcome-specific denominator

  • 12 — unique participants; scope: crossover study

CI not supplied in the verified scope.

Reported p-value: <0.04 (between condition comparison)

Subjective hunger

Sleep restriction versus extension

Effect estimate

24 % relative difference

reported relative difference

Unit: % relative difference

After two days in each experimental condition

Reported N: 12 — unique crossover-study participants; not an outcome-specific denominator

  • 12 — unique participants; scope: crossover study

CI not supplied in the verified scope.

Reported p-value: <0.01 (between condition comparison)

Mean leptin — Sleep restriction versus extension: extraction context
Outcome role
Not specified in the consulted scope
Scale reference
relative_to_sleep_extension_condition
Extraction location
Original article abstract
  • The same participants experienced both conditions; do not count them as 24 people.
Mean ghrelin — Sleep restriction versus extension: extraction context
Outcome role
Not specified in the consulted scope
Scale reference
relative_to_sleep_extension_condition
Extraction location
Original article abstract
  • The same participants experienced both conditions; do not count them as 24 people.
Subjective hunger — Sleep restriction versus extension: extraction context
Outcome role
Not specified in the consulted scope
Scale reference
relative_to_sleep_extension_condition
Extraction location
Original article abstract
  • The same participants experienced both conditions; do not count them as 24 people.

What the curated evidence supports

  • In a crossover experiment involving 12 young men, restricted sleep was associated with 18% lower leptin, 28% higher ghrelin and 24% greater subjective hunger than sleep extension.

Limitations

  • Only 12 young men, with two two-day conditions; not representative of all populations.
  • It does not establish future weight gain or a universal hormonal pattern.

Verification scope

Verified through 2026-11-04 within the consulted scope.

Bibliographic metadata checked
Yes
Original article abstract consulted
Yes
Full-text consultation
Not consulted
full text verified fields
    Official trial registry consulted
    No
    Statistical analysis plan consulted
    No
    Verification boundary
    Verification is limited to the input's identified abstract/full-text fields. A trial identifier linked by an article does not imply a separate registry review.

    Source record

    Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite (2004)

    Source identifiers

    • PubMed record 15583226
    • Article DOI: 10.7326/0003-4819-141-11-200412070-00008

    Controlled study

    Acute stress, cortisol and intake: the Geliebter experiment

    In Geliebter's experiment involving 20 women with obesity, comparing a cold pressor with warm water on counterbalanced days, no statistically significant relationship was found between the cortisol response and food intake.

    Evidence design
    Controlled, counterbalanced crossover experiment; order randomization unverified
    Population
    Twenty women with obesity, assessed while fasting and after an acute laboratory stressor.

    Keep in view

    • Experiment in 20 women; counterbalanced days, with order randomization unverified in the consulted scope.
    • A statistically nonsignificant association does not establish the absence of any relationship.
    • Do not extrapolate the acute laboratory stressor to chronic stress or weight loss.
    See study details — Cortisol and intake experiment

    Study design and methods

    Controlled, counterbalanced crossover experiment; order randomization unverified

    Controlled crossover experiment on two counterbalanced days: a hand in ice-cold water for two minutes versus warm water. Random assignment of the order was not confirmed; do not label it a randomized trial.

    Population

    Twenty women with obesity, assessed while fasting and after an acute laboratory stressor.

    Study design
    Controlled crossover experiment on two counterbalanced days: a hand in ice-cold water for two minutes versus warm water. Random assignment of the order was not confirmed; do not label it a randomized trial.
    Reported sample count
    20
    Role of the reported sample count
    Reported study sample; not necessarily the denominator for each outcome
    Included study count
    1
    Role of the study count
    Single study
    Research question
    Does the cortisol response to an acute stressor predict appetite or intake at a subsequent meal?
    Qualified findings
    The ice-cold-water test increased cortisol and perceived stress but did not increase intake at the test meal. Hunger and desire to eat decreased in acute measurements; cortisol concentration did not show a significant relationship with subsequent intake in this experiment.
    Estimand and analysis rules
    Not reported or not verified
    Reason the formal estimand is unavailable
    A complete formal estimand was not extracted from the verified input.

    What the curated evidence supports

    • In Geliebter's experiment involving 20 women with obesity, comparing a cold pressor with warm water on counterbalanced days, no statistically significant relationship was found between the cortisol response and food intake.

    Limitations

    • Experiment in 20 women; counterbalanced days, with order randomization unverified in the consulted scope.
    • A statistically nonsignificant association does not establish the absence of any relationship.
    • Do not extrapolate the acute laboratory stressor to chronic stress or weight loss.

    Verification scope

    Verified through 2026-11-04 within the consulted scope.

    Bibliographic metadata checked
    Yes
    Original article abstract consulted
    Yes
    Full-text consultation
    Not consulted
    full text verified fields
      Official trial registry consulted
      No
      Statistical analysis plan consulted
      No
      Verification boundary
      Verification is limited to the input's identified abstract/full-text fields. A trial identifier linked by an article does not imply a separate registry review.

      Source record

      Plasma cortisol levels in response to a cold pressor test did not predict appetite or ad libitum test meal intake in obese women (2012)

      Source identifiers

      • PubMed record 22983369
      • PubMed Central: PMC3490010
      • Article DOI: 10.1016/j.appet.2012.08.025

      Evidence review

      Stress and eating: average associations in the Hill review

      In Hill's review, stress showed small average associations with higher total intake (g=0.114), greater intake of foods the studies classified as less healthy (g=0.116), and lower intake of foods classified as healthy (g=−0.111).

      Evidence design
      Systematic review and meta-analysis
      Population
      Healthy adults; explicitly defined stress measures and varied eating behaviors.
      Assessment period
      Varying protocols and time points across the review
      Reported units
      Hedges’ g

      Keep in view

      • Small average effects and between-study heterogeneity; not everyone's response.
      • 119,820 is the review-wide total; each effect's denominator was not verified.
      • Food categories come from the studies; they do not morally characterize people who eat them.
      • It does not establish cortisol as a causal mediator.
      See study details — Stress and eating review

      Review design and extraction scope

      Systematic review and meta-analysis

      Systematic review and meta-analysis of 54 studies on stress and non-disordered eating.

      Population

      Healthy adults; explicitly defined stress measures and varied eating behaviors.

      Study design
      Systematic review and meta-analysis of 54 studies on stress and non-disordered eating.
      Reported sample count
      119820
      Role of the reported sample count
      Review-wide total; not an outcome-specific denominator
      Included study count
      54
      Role of the study count
      Review-wide total; not an outcome-specific denominator
      Research question
      What is the magnitude of the relationship between stress and total intake or food choices?
      Qualified findings
      Stress was associated with a small average increase in intake and in consumption of foods classified as less healthy, and with lower consumption of those classified as healthy. Significant heterogeneity was not explained by the moderators examined.
      Estimand and analysis rules
      Not reported or not verified
      Reason the formal estimand is unavailable
      A complete formal estimand was not extracted from the verified input.

      How to read this review

      Included studies may differ in population, design and outcomes. Review-wide counts describe coverage and cannot be used as the sample size of every estimate.

      Included studies: 54 — Review-wide total; not an outcome-specific denominator.

      Extracted review results and scope

      Study counts describe review scope. Review-wide participant totals are not outcome-specific denominators.

      Reported values, analysis populations and uncertainty, preserved from the curated extraction.
      Outcome and groupReported valueAssessment periodSample and denominatorsUncertainty
      Association with total intake

      Stress–eating association

      Effect estimate

      		0.114 Hedges’ g

      standardized association

      Unit: Hedges’ g

      		Varying protocols and time points across the review

      Reported N: 119820 — review-wide participants; not an outcome-specific denominator

      • 119820 — review total participants; scope: all review studies
      • 54 — review total studies; scope: all review studies
      • Not reported or not verified — outcome specific participants; scope: total intake association
      • Not reported or not verified — outcome specific studies; scope: total intake association

      Each effect's CI and denominator were not verified in the abstract.

      Association with foods classified as less healthy in the studies

      Stress–eating association

      Effect estimate

      		0.116 Hedges’ g

      standardized association

      Unit: Hedges’ g

      		Varying protocols and time points across the review

      Reported N: 119820 — review-wide participants; not an outcome-specific denominator

      • 119820 — review total participants; scope: all review studies
      • 54 — review total studies; scope: all review studies
      • Not reported or not verified — outcome specific participants; scope: study defined less healthy food intake
      • Not reported or not verified — outcome specific studies; scope: study defined less healthy food intake

      Each effect's CI and denominator were not verified in the abstract.

      Association with foods classified as healthy in the studies

      Stress–eating association

      Effect estimate

      		-0.111 Hedges’ g

      standardized association

      Unit: Hedges’ g

      		Varying protocols and time points across the review

      Reported N: 119820 — review-wide participants; not an outcome-specific denominator

      • 119820 — review total participants; scope: all review studies
      • 54 — review total studies; scope: all review studies
      • Not reported or not verified — outcome specific participants; scope: study defined healthier food intake
      • Not reported or not verified — outcome specific studies; scope: study defined healthier food intake

      Each effect's CI and denominator were not verified in the abstract.

      Association with total intake — Stress–eating association: extraction context
      Outcome role
      Not specified in the consulted scope
      Scale reference
      standardized_effect
      Extraction location
      Original systematic-review abstract
      • Synthesis of varied designs; do not interpret it as one causal trial.
      Association with foods classified as less healthy in the studies — Stress–eating association: extraction context
      Outcome role
      Not specified in the consulted scope
      Scale reference
      standardized_effect
      Extraction location
      Original systematic-review abstract
      • Synthesis of varied designs; do not interpret it as one causal trial.
      Association with foods classified as healthy in the studies — Stress–eating association: extraction context
      Outcome role
      Not specified in the consulted scope
      Scale reference
      standardized_effect
      Extraction location
      Original systematic-review abstract
      • Synthesis of varied designs; do not interpret it as one causal trial.

      What the curated evidence supports

      • In Hill's review, stress showed small average associations with higher total intake (g=0.114), greater intake of foods the studies classified as less healthy (g=0.116), and lower intake of foods classified as healthy (g=−0.111).

      Limitations

      • Small average effects and between-study heterogeneity; not everyone's response.
      • 119,820 is the review-wide total; each effect's denominator was not verified.
      • Food categories come from the studies; they do not morally characterize people who eat them.
      • It does not establish cortisol as a causal mediator.

      Verification scope

      Verified through 2026-11-04 within the consulted scope.

      Bibliographic metadata checked
      Yes
      Original article abstract consulted
      Yes
      Full-text consultation
      Not consulted
      full text verified fields
        Official trial registry consulted
        No
        Statistical analysis plan consulted
        No
        Verification boundary
        Verification is limited to the input's identified abstract/full-text fields. A trial identifier linked by an article does not imply a separate registry review.

        Source record

        Stress and eating behaviours in healthy adults: a systematic review and meta-analysis (2022)

        Source identifiers

        • PubMed record 33913377
        • Article DOI: 10.1080/17437199.2021.1923406

        Evidence review

        Sleep duration, food intake and hormones: a trial review

        The review of 50 trials found indications of greater intake, hunger and appetite with sleep restriction, but not a consistent pattern of changes in leptin, ghrelin and cortisol.

        Evidence design
        Systematic review of randomized clinical trials
        Population
        Adults, children and adolescents; varied populations and experimental conditions.
        Assessment period
        Study count, with no single intervention duration
        Reported units
        trials

        Keep in view

        • Protocols and age groups varied; no single verified magnitude applies to all outcomes.
        • 50 counts trials, not participants or the denominator for each outcome.
        • Reviews may share trials; do not sum their samples as independent evidence.
        See study details — Sleep restriction review

        Review design and extraction scope

        Systematic review of randomized clinical trials

        Systematic review of randomized trials; search through July 2020.

        Population

        Adults, children and adolescents; varied populations and experimental conditions.

        Study design
        Systematic review of randomized trials; search through July 2020.
        Reported sample count
        Not reported or not verified
        Role of the reported sample count
        Review-wide total; not an outcome-specific denominator
        Included study count
        50
        Role of the study count
        Review-wide total; not an outcome-specific denominator
        Research question
        How does sleep duration affect intake, desire to eat, body measurements and hormones?
        Qualified findings
        The review suggests greater intake, hunger and appetite with sleep restriction. The synthesis did not identify a consistent influence on leptin, ghrelin and cortisol. This supports cautious wording about hormonal mechanisms.
        Estimand and analysis rules
        Not reported or not verified
        Reason the formal estimand is unavailable
        A complete formal estimand was not extracted from the verified input.

        How to read this review

        Included studies may differ in population, design and outcomes. Review-wide counts describe coverage and cannot be used as the sample size of every estimate.

        Included studies: 50 — Review-wide total; not an outcome-specific denominator.

        Extracted review results and scope

        Study counts describe review scope. Review-wide participant totals are not outcome-specific denominators.

        Reported values, analysis populations and uncertainty, preserved from the curated extraction.
        Outcome and groupReported valueAssessment periodSample and denominatorsUncertainty
        Trials included in the review

        Review scope

        Review scope count; not a clinical effect

        		50 trials

        Included study count

        Unit: trials

        		Study count, with no single intervention duration

        Participant N: not applicable to a study count

        • Not reported or not verified — review total participants not verified; scope: review

        Review-scope count, not an estimated effect; a CI is not applicable.

        Trials included in the review — Review scope: extraction context
        Outcome role
        Not specified in the consulted scope
        Extraction location
        Original systematic-review abstract
        • 43 adult trials and seven child/adolescent trials; do not use 50 as a participant denominator.

        What the curated evidence supports

        • The review of 50 trials found indications of greater intake, hunger and appetite with sleep restriction, but not a consistent pattern of changes in leptin, ghrelin and cortisol.

        Limitations

        • Protocols and age groups varied; no single verified magnitude applies to all outcomes.
        • 50 counts trials, not participants or the denominator for each outcome.
        • Reviews may share trials; do not sum their samples as independent evidence.

        Verification scope

        Verified through 2026-11-04 within the consulted scope.

        Bibliographic metadata checked
        Yes
        Original article abstract consulted
        Yes
        Full-text consultation
        Not consulted
        full text verified fields
          Official trial registry consulted
          No
          Statistical analysis plan consulted
          No
          Verification boundary
          Verification is limited to the input's identified abstract/full-text fields. A trial identifier linked by an article does not imply a separate registry review.

          Source record

          Effect of sleep duration on dietary intake, desire to eat, measures of food intake and metabolic hormones: A systematic review of clinical trials (2021)

          Source identifiers

          • PubMed record 34620371
          • Article DOI: 10.1016/j.clnesp.2021.07.029

          Controlled study

          Sleep extension and energy intake: the Tasali trial

          In Tasali's trial involving 80 adults with overweight and short sleep, two weeks of sleep extension produced a −270 kcal/day difference in the change in estimated energy intake relative to control (95% CI −393 to −147).

          In the same trial, the difference in sleep duration was 1.2 hours per night in favor of the intervention (95% CI 1.0–1.4).

          Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Evidence design
          Randomized parallel clinical trial
          Population
          Adults aged 21–40 years, with BMI 25.0–29.9 kg/m² and habitual sleep shorter than 6.5 h/night.
          Assessment period
          Two intervention weeks following two baseline weeks
          Reported units
          kcal/day; hours/night

          Keep in view

          • 80 adults aged 21–40 with overweight and habitual sleep shorter than 6.5 hours; single center.
          • Two intervention weeks do not establish sustained weight-loss maintenance.
          • Intake was estimated from energy balance, not measured by directly counting food.
          See study details — Sleep extension trial

          Study design and methods

          Randomized parallel clinical trial

          Single-center randomized trial; two baseline weeks and two intervention weeks in the usual environment; intention-to-treat analysis.

          Population

          Adults aged 21–40 years, with BMI 25.0–29.9 kg/m² and habitual sleep shorter than 6.5 h/night.

          Study design
          Single-center randomized trial; two baseline weeks and two intervention weeks in the usual environment; intention-to-treat analysis.
          Reported sample count
          80
          Role of the reported sample count
          Reported study sample; not necessarily the denominator for each outcome
          Included study count
          1
          Role of the study count
          Single study
          Research question
          Does extending sleep reduce objectively estimated energy intake in adults with overweight and short sleep?
          Qualified findings
          Counseling to extend sleep increased sleep duration and reduced estimated intake compared with control. Total expenditure did not differ significantly. This is a two-week finding; it does not demonstrate weight-loss maintenance.
          Estimand and analysis rules
          Not reported or not verified
          Reason the formal estimand is unavailable
          A complete formal estimand was not extracted from the verified input.

          Extracted outcomes

          Reported values, analysis populations and uncertainty, preserved from the curated extraction.
          Outcome and groupReported valueAssessment periodSample and denominatorsUncertainty
          Sleep duration

          Sleep extension minus control

          Effect estimate

          		1.2 hours/night

          reported between-group change difference

          Unit: hours/night

          		Two intervention weeks following two baseline weeks

          Reported N: 80 — total randomized trial sample; not a group denominator

          • 80 — randomized total; scope: trial

          95% confidence interval: 1 to 1.4

          Reported p-value: <0.001 (Between-group comparison)

          Estimated energy intake

          Sleep extension minus control

          Effect estimate

          		-270 kcal/day

          reported between-group change difference

          Unit: kcal/day

          		Two intervention weeks following two baseline weeks

          Reported N: 80 — total randomized trial sample; not a group denominator

          • 80 — randomized total; scope: trial

          95% confidence interval: -393 to -147

          Reported p-value: <0.001 (Between-group comparison)

          Sleep duration — Sleep extension minus control: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          intervention_vs_control_change
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis population
          Intention-to-treat, as described in the verified input
          formal estimand not extracted
          Yes
          Extraction location
          Original article abstract; intervention duration checked in PMC full text
          • N=80 is the trial total; arm sizes and effect-specific N were not extracted.
          Estimated energy intake — Sleep extension minus control: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          intervention_vs_control_change
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis population
          Intention-to-treat, as described in the verified input
          formal estimand not extracted
          Yes
          Extraction location
          Original article abstract; intervention duration checked in PMC full text
          • N=80 is the trial total; arm sizes and effect-specific N were not extracted.

          What the curated evidence supports

          • In Tasali's trial involving 80 adults with overweight and short sleep, two weeks of sleep extension produced a −270 kcal/day difference in the change in estimated energy intake relative to control (95% CI −393 to −147).
          • In the same trial, the difference in sleep duration was 1.2 hours per night in favor of the intervention (95% CI 1.0–1.4).
          • Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Limitations

          • 80 adults aged 21–40 with overweight and habitual sleep shorter than 6.5 hours; single center.
          • Two intervention weeks do not establish sustained weight-loss maintenance.
          • Intake was estimated from energy balance, not measured by directly counting food.

          Verification scope

          Verified through 2026-11-04 within the consulted scope.

          Bibliographic metadata checked
          Yes
          Original article abstract consulted
          Yes
          Full-text consultation
          selected_fields_only
          full text verified fields
          • intervention_duration
          • pmcid_linkage
          Official trial registry consulted
          No
          Statistical analysis plan consulted
          No
          Verification boundary
          Verification is limited to the input's identified abstract/full-text fields. A trial identifier linked by an article does not imply a separate registry review.

          Source record

          Effect of Sleep Extension on Objectively Assessed Energy Intake Among Adults With Overweight in Real-life Settings: A Randomized Clinical Trial (2022)

          Source identifiers

          • PubMed record 35129580
          • PubMed Central: PMC8822469
          • Article DOI: 10.1001/jamainternmed.2021.8098

          Controlled study

          STEP 1: weight change at 68 weeks

          In STEP 1, mean weight change was −14.9% with semaglutide and −2.4% with placebo at 68 weeks; the published adjusted difference was −12.4 percentage points (95% CI −13.4 to −11.5).

          The STEP 1 abstract reports discontinuation due to gastrointestinal events in 59 participants (4.5%) receiving semaglutide and five (0.8%) receiving placebo.

          Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Evidence design
          Randomized comparison
          Population
          Adults without diabetes with BMI >=30 kg/m2, or >=27 kg/m2 with at least one weight-related coexisting condition; lifestyle intervention in both groups.
          Assessment period
          Baseline to week 68; During the trial; precise safety window not verified
          Reported units
          percentage points; % change; %

          Keep in view

          • The result concerns 68 weeks of treatment; it does not establish maintenance after withdrawal.
          • The published adjusted difference is −12.4 pp and must not be replaced by subtraction of rounded arm means.
          See study details — STEP 1

          Study design and methods

          Randomized comparison

          Randomized, double-blind, placebo-controlled trial; allocation 2:1; 68 weeks; phase 3.

          Population

          Adults without diabetes with BMI >=30 kg/m2, or >=27 kg/m2 with at least one weight-related coexisting condition; lifestyle intervention in both groups.

          Outcome definition
          Percent change in body weight from baseline
          Assessment period
          Value
          68
          Unit
          weeks
          Reported statistic
          Mean
          Unit
          % change from baseline
          Randomized participants
          1961
          Estimand and analysis rules
          Name
          treatment-policy primary estimand
          Definition
          Treatment effect assessed regardless of treatment discontinuation or rescue interventions, as described in the primary publication abstract.
          Analysis population
          FAS consists of all randomized participants (1306 semaglutide; 655 placebo).

          Extracted outcomes

          Reported values, analysis populations and uncertainty, preserved from the curated extraction.
          Outcome and groupReported valueAssessment periodSample and denominatorsUncertainty
          Percent change in body weight

          Semaglutide

          Effect estimate

          		-14.9 % change

          Mean

          Unit: % change

          		Baseline to week 68

          Study weeks 0–68

          Reported N: 1306 — full analysis population

          • 1961 — randomized total; scope: entire trial
          • 1306 — randomized group; scope: Semaglutide

          Arm confidence interval not verified; no reconstruction was performed.

          Percent change in body weight

          Placebo

          Effect estimate

          		-2.4 % change

          Mean

          Unit: % change

          		Baseline to week 68

          Study weeks 0–68

          Reported N: 655 — full analysis population

          • 1961 — randomized total; scope: entire trial
          • 655 — randomized group; scope: Placebo

          Arm confidence interval not verified; no reconstruction was performed.

          Percent change in body weight

          Semaglutide minus placebo

          Effect estimate

          		-12.4 percentage points

          adjusted mean difference

          Unit: percentage points

          		Baseline to week 68

          Study weeks 0–68

          Reported N: 1961 — combined full analysis population

          • 1961 — randomized total; scope: entire trial

          95% confidence interval: -13.4 to -11.5

          Reported p-value: <0.001 (Between-group comparison)

          Discontinuation due to gastrointestinal events

          Semaglutide 2.4 mg weekly

          Descriptive result; not an effect estimate

          		4.5 %

          reported event percentage

          Exact numerator: 59

          Unit: %

          		During the trial; precise safety window not verified

          Reported N: Not reported or not verified — outcome-specific denominator not verified

          • 1306 — randomized arm context only; scope: Semaglutide

          Confidence interval for this event was not verified; descriptive count or percentage.

          Discontinuation due to gastrointestinal events

          Placebo

          Descriptive result; not an effect estimate

          		0.8 %

          reported event percentage

          Exact numerator: 5

          Unit: %

          		During the trial; precise safety window not verified

          Reported N: Not reported or not verified — outcome-specific denominator not verified

          • 655 — randomized arm context only; scope: Placebo

          Confidence interval for this event was not verified; descriptive count or percentage.

          Percent change in body weight — Semaglutide: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          baseline_body_weight
          Estimand and analysis rules
          Name
          treatment-policy primary estimand
          Definition
          Treatment effect assessed regardless of treatment discontinuation or rescue interventions, as described in the primary publication abstract.
          Extraction location
          Original article abstract; arm sample sizes cross-checked against registry participant flow
          Percent change in body weight — Placebo: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          baseline_body_weight
          Estimand and analysis rules
          Name
          treatment-policy primary estimand
          Definition
          Treatment effect assessed regardless of treatment discontinuation or rescue interventions, as described in the primary publication abstract.
          Extraction location
          Original article abstract; arm sample sizes cross-checked against registry participant flow
          Percent change in body weight — Semaglutide minus placebo: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          Difference in percent change
          Estimand and analysis rules
          Name
          treatment-policy primary estimand
          Definition
          Treatment effect assessed regardless of treatment discontinuation or rescue interventions, as described in the primary publication abstract.
          Extraction location
          Published comparison; SURMOUNT-5 contrast CI verified in official registry
          • Reported difference; not recomputed from rounded arm means.
          Discontinuation due to gastrointestinal events — Semaglutide 2.4 mg weekly: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          Original article abstract, safety results
          • The safety denominator was not inferred from the randomized arm size.
          Discontinuation due to gastrointestinal events — Placebo: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          Original article abstract, safety results
          • The safety denominator was not inferred from the randomized arm size.

          What the curated evidence supports

          • In STEP 1, mean weight change was −14.9% with semaglutide and −2.4% with placebo at 68 weeks; the published adjusted difference was −12.4 percentage points (95% CI −13.4 to −11.5).
          • The STEP 1 abstract reports discontinuation due to gastrointestinal events in 59 participants (4.5%) receiving semaglutide and five (0.8%) receiving placebo.
          • Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Limitations

          • The result concerns 68 weeks of treatment; it does not establish maintenance after withdrawal.
          • The published adjusted difference is −12.4 pp and must not be replaced by subtraction of rounded arm means.

          Verification scope

          Verified through 2026-11-04 within the consulted scope.

          Bibliographic metadata checked
          Yes
          Original article abstract consulted
          Yes
          Full-text consultation
          Not consulted
          Official trial registry consulted
          Yes
          Statistical analysis plan consulted
          No
          Verification boundary
          Verification is limited to the specific fields and sources consulted; it is not a full systematic appraisal or GRADE rating.

          Source record

          Once-Weekly Semaglutide in Adults with Overweight or Obesity (2021). The New England journal of medicine.

          Source identifiers

          • Article DOI: 10.1056/NEJMoa2032183
          • PubMed record 33567185
          • Trial registration: NCT03548935
          • Structured registry: NCT03548935

          Controlled study

          SURMOUNT-1 DXA: weight, fat and lean soft tissue at 72 weeks

          The DXA substudy analyzed 160 participants: 124 receiving pooled tirzepatide doses and 36 receiving placebo. At 72 weeks, changes in weight, fat and lean mass were −21.3%, −33.9% and −10.9% with tirzepatide, versus −5.3%, −8.2% and −2.6% with placebo.

          In this analysis, DXA lean mass is fat-free mass minus bone mineral content. It includes tissues other than muscle and, alone, does not describe strength or diagnose sarcopenia.

          The article describes roughly three quarters of combined fat and lean mass losses as fat. This sample-level composition does not justify saying that one quarter of lost weight was skeletal muscle.

          Evidence design
          Randomized trial substudy
          Population
          Subset of SURMOUNT-1 adults with obesity or overweight and a weight-related complication, without type 2 diabetes; 73.1% female; mean age 46.2 years, weight 102.5 kg and BMI 38.0 kg/m2.
          Assessment period
          Baseline to week 72
          Reported units
          percentage points; % change; % of combined fat and lean mass loss; kg

          Keep in view

          • 160 of 255 substudy enrollees were analyzed; 5, 10 and 15 mg doses were pooled.
          • DXA lean mass does not directly measure skeletal muscle or strength.
          • There was no multiplicity adjustment; missing data from three participants used last observation carried forward.
          See study details — SURMOUNT-1 DXA

          Study design and methods

          Randomized trial substudy

          Prespecified DXA body-composition substudy nested within randomized SURMOUNT-1; pooled tirzepatide doses; additional post hoc subgroup analyses.

          Population

          Subset of SURMOUNT-1 adults with obesity or overweight and a weight-related complication, without type 2 diabetes; 73.1% female; mean age 46.2 years, weight 102.5 kg and BMI 38.0 kg/m2.

          Assessment period
          Value
          72
          Unit
          weeks
          Parent trial randomized participants
          2539
          Substudy enrollees
          255
          Substudy analyzed participants
          160
          Analyzed participants by arm
          Tirzepatide, pooled doses
          124
          Placebo
          36
          Analysis denominator basis
          Participants in the substudy who were randomized, received >=1 dose and had nonmissing baseline and postbaseline DXA measurements. Of 255 enrolled, 160 completed baseline and week-72 or early-discontinuation scans and were included.
          Dose pooling
          5, 10 and 15 mg tirzepatide pooled; these results cannot be relabeled as a 15-mg-only effect.
          Measurement definition
          Measurement method
          Whole-body dual-energy X-ray absorptiometry (DXA)
          Measurement timing
          Baseline before first dose and end of treatment at week 72 (within 14 days) or early discontinuation.
          DXA lean mass definition
          DXA lean mass = fat-free mass minus total bone mineral content. It is lean soft tissue, not a direct skeletal-muscle measurement.
          Fat-free mass definition
          Includes nonfat tissues such as muscle, bone, organs, ligaments, tendons and water; fat-free mass itself was not the reported endpoint.
          Skeletal muscle measured directly
          No
          Direct strength or physical-performance outcome in this card
          No
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes

          Extracted outcomes

          Reported values, analysis populations and uncertainty, preserved from the curated extraction.
          Outcome and groupReported valueAssessment periodSample and denominatorsUncertainty
          Percent change in body weight

          Tirzepatide pooled 5/10/15 mg

          Effect estimate

          		-21.3 % change

          least-squares mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 124 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 124 — substudy analysis arm; scope: Tirzepatide, pooled doses

          Arm confidence interval not verified; no reconstruction was performed.

          Percent change in body weight

          Placebo

          Effect estimate

          		-5.3 % change

          least-squares mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 36 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 36 — substudy analysis arm; scope: Placebo

          Arm confidence interval not verified; no reconstruction was performed.

          Percent change in body weight

          Pooled tirzepatide minus placebo

          Effect estimate

          		-16 percentage points

          adjusted mean difference

          Unit: percentage points

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 160 — combined substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy

          95% confidence interval: -19.4 to -12.6

          Reported p-value: <0.001 (between group comparison no multiplicity adjustment)

          Percent change in fat mass

          Tirzepatide pooled 5/10/15 mg

          Effect estimate

          		-33.9 % change

          least-squares mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 124 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 124 — substudy analysis arm; scope: Tirzepatide, pooled doses

          Arm confidence interval not verified; no reconstruction was performed.

          Percent change in fat mass

          Placebo

          Effect estimate

          		-8.2 % change

          least-squares mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 36 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 36 — substudy analysis arm; scope: Placebo

          Arm confidence interval not verified; no reconstruction was performed.

          Percent change in fat mass

          Pooled tirzepatide minus placebo

          Effect estimate

          		-25.7 percentage points

          adjusted mean difference

          Unit: percentage points

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 160 — combined substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy

          95% confidence interval: -31.4 to -20

          Reported p-value: <0.001 (between group comparison no multiplicity adjustment)

          Percent change in DXA lean soft tissue mass

          Tirzepatide pooled 5/10/15 mg

          Effect estimate

          		-10.9 % change

          least-squares mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 124 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 124 — substudy analysis arm; scope: Tirzepatide, pooled doses

          Arm confidence interval not verified; no reconstruction was performed.

          Percent change in DXA lean soft tissue mass

          Placebo

          Effect estimate

          		-2.6 % change

          least-squares mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 36 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 36 — substudy analysis arm; scope: Placebo

          Arm confidence interval not verified; no reconstruction was performed.

          Percent change in DXA lean soft tissue mass

          Pooled tirzepatide minus placebo

          Effect estimate

          		-8.3 percentage points

          adjusted mean difference

          Unit: percentage points

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 160 — combined substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy

          95% confidence interval: -10.6 to -6.1

          Reported p-value: <0.001 (between group comparison no multiplicity adjustment)

          Absolute change in fat mass

          Tirzepatide pooled 5/10/15 mg

          Effect estimate

          		-15.9 kg

          least-squares mean

          Unit: kg

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 124 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 124 — substudy analysis arm; scope: Tirzepatide, pooled doses

          Arm confidence interval not verified; no reconstruction was performed.

          Absolute change in fat mass

          Placebo

          Effect estimate

          		-3.6 kg

          least-squares mean

          Unit: kg

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 36 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 36 — substudy analysis arm; scope: Placebo

          Arm confidence interval not verified; no reconstruction was performed.

          Absolute change in fat mass

          Pooled tirzepatide minus placebo

          Effect estimate

          		-12.3 kg

          adjusted mean difference

          Unit: kg

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 160 — combined substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy

          95% confidence interval: -15.1 to -9.6

          Reported p-value: <0.001 (between group comparison no multiplicity adjustment)

          Absolute change in DXA lean soft tissue mass

          Tirzepatide pooled 5/10/15 mg

          Effect estimate

          		-5.6 kg

          least-squares mean

          Unit: kg

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 124 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 124 — substudy analysis arm; scope: Tirzepatide, pooled doses

          Arm confidence interval not verified; no reconstruction was performed.

          Absolute change in DXA lean soft tissue mass

          Placebo

          Effect estimate

          		-1.2 kg

          least-squares mean

          Unit: kg

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 36 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy
          • 36 — substudy analysis arm; scope: Placebo

          Arm confidence interval not verified; no reconstruction was performed.

          Absolute change in DXA lean soft tissue mass

          Pooled tirzepatide minus placebo

          Effect estimate

          		-4.4 kg

          adjusted mean difference

          Unit: kg

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 160 — combined substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy

          95% confidence interval: -5.6 to -3.2

          Reported p-value: <0.001 (between group comparison no multiplicity adjustment)

          Fat fraction of combined fat and lean mass losses

          Pooled tirzepatide

          Descriptive result; not an effect estimate

          		74 % of combined fat and lean mass loss

          reported proportion

          Unit: % of combined fat and lean mass loss

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 124 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy

          Confidence interval for the fraction not verified.

          Lean soft tissue fraction of combined fat and lean mass losses

          Pooled tirzepatide

          Descriptive result; not an effect estimate

          		26 % of combined fat and lean mass loss

          reported proportion

          Unit: % of combined fat and lean mass loss

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 124 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy

          Confidence interval for the fraction not verified.

          Fat fraction of combined fat and lean mass losses

          Placebo

          Descriptive result; not an effect estimate

          		75 % of combined fat and lean mass loss

          reported proportion

          Unit: % of combined fat and lean mass loss

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 36 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy

          Confidence interval for the fraction not verified.

          Lean soft tissue fraction of combined fat and lean mass losses

          Placebo

          Descriptive result; not an effect estimate

          		25 % of combined fat and lean mass loss

          reported proportion

          Unit: % of combined fat and lean mass loss

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 36 — substudy analysis population

          • 2539 — parent trial randomized total; scope: parent trial
          • 255 — substudy enrolled; scope: DXA substudy
          • 160 — substudy analyzed; scope: DXA substudy

          Confidence interval for the fraction not verified.

          Percent change in body weight — Tirzepatide pooled 5/10/15 mg: extraction context
          Outcome role
          Exploratory, post hoc
          Scale reference
          Baseline value of the same tissue or weight
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          Percent change in body weight — Placebo: extraction context
          Outcome role
          Exploratory, post hoc
          Scale reference
          Baseline value of the same tissue or weight
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          Percent change in body weight — Pooled tirzepatide minus placebo: extraction context
          Outcome role
          Exploratory, post hoc
          Scale reference
          Difference in percent change
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2
          • No multiplicity adjustment.
          Percent change in fat mass — Tirzepatide pooled 5/10/15 mg: extraction context
          Outcome role
          primary_substudy_objective
          Scale reference
          Baseline value of the same tissue or weight
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          Percent change in fat mass — Placebo: extraction context
          Outcome role
          primary_substudy_objective
          Scale reference
          Baseline value of the same tissue or weight
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          Percent change in fat mass — Pooled tirzepatide minus placebo: extraction context
          Outcome role
          primary_substudy_objective
          Scale reference
          Difference in percent change
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2
          • No multiplicity adjustment.
          Percent change in DXA lean soft tissue mass — Tirzepatide pooled 5/10/15 mg: extraction context
          Outcome role
          secondary
          Scale reference
          Baseline value of the same tissue or weight
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          • Lean mass means lean soft tissue excluding bone mineral content; it is not skeletal muscle mass.
          Percent change in DXA lean soft tissue mass — Placebo: extraction context
          Outcome role
          secondary
          Scale reference
          Baseline value of the same tissue or weight
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          • Lean mass means lean soft tissue excluding bone mineral content; it is not skeletal muscle mass.
          Percent change in DXA lean soft tissue mass — Pooled tirzepatide minus placebo: extraction context
          Outcome role
          secondary
          Scale reference
          Difference in percent change
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2
          • No multiplicity adjustment.
          Absolute change in fat mass — Tirzepatide pooled 5/10/15 mg: extraction context
          Outcome role
          secondary
          Scale reference
          absolute_change
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          Absolute change in fat mass — Placebo: extraction context
          Outcome role
          secondary
          Scale reference
          absolute_change
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          Absolute change in fat mass — Pooled tirzepatide minus placebo: extraction context
          Outcome role
          secondary
          Scale reference
          absolute_difference
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2
          • No multiplicity adjustment.
          Absolute change in DXA lean soft tissue mass — Tirzepatide pooled 5/10/15 mg: extraction context
          Outcome role
          secondary
          Scale reference
          absolute_change
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          • Lean mass means lean soft tissue excluding bone mineral content; it is not skeletal muscle mass.
          Absolute change in DXA lean soft tissue mass — Placebo: extraction context
          Outcome role
          secondary
          Scale reference
          absolute_change
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2; Figure 1 or supplementary Figure S2
          • Lean mass means lean soft tissue excluding bone mineral content; it is not skeletal muscle mass.
          Absolute change in DXA lean soft tissue mass — Pooled tirzepatide minus placebo: extraction context
          Outcome role
          secondary
          Scale reference
          absolute_difference
          Estimand and analysis rules
          Name
          Not reported or not verified
          Analysis set
          Modified intention-to-treat population (efficacy analysis set)
          Definition verification status
          Full formal estimand not verified; do not inherit the parent-trial treatment-regimen estimand.
          Statistical analysis
          Analysis population label in the figure
          Modified intention-to-treat population (efficacy analysis set)
          Statistical model
          ANCOVA for body weight, fat and lean measures: baseline response covariate and treatment factor; waist used MMRM.
          Missing-data handling
          Three missing week-72 observations imputed by last observation carried forward.
          Multiplicity adjustment
          No
          Formal estimand specification
          Efficacy analysis set; a separate, fully specified five-attribute estimand was not verified in the substudy full text.
          Parent-trial estimand must not be inherited without qualification
          Yes
          Extraction location
          Full text section 3.2
          • No multiplicity adjustment.
          Fat fraction of combined fat and lean mass losses — Pooled tirzepatide: extraction context
          Outcome role
          Exploratory, post hoc
          Scale reference
          fat_loss_plus_lean_mass_loss
          Extraction location
          Full text Table 1 formula and section 3.2
          • Fraction of combined fat and lean mass losses; not a skeletal-muscle fraction or an individual prediction.
          Lean soft tissue fraction of combined fat and lean mass losses — Pooled tirzepatide: extraction context
          Outcome role
          Exploratory, post hoc
          Scale reference
          fat_loss_plus_lean_mass_loss
          Extraction location
          Full text Table 1 formula and section 3.2
          • Fraction of combined fat and lean mass losses; not a skeletal-muscle fraction or an individual prediction.
          Fat fraction of combined fat and lean mass losses — Placebo: extraction context
          Outcome role
          Exploratory, post hoc
          Scale reference
          fat_loss_plus_lean_mass_loss
          Extraction location
          Full text Table 1 formula and section 3.2
          • Fraction of combined fat and lean mass losses; not a skeletal-muscle fraction or an individual prediction.
          Lean soft tissue fraction of combined fat and lean mass losses — Placebo: extraction context
          Outcome role
          Exploratory, post hoc
          Scale reference
          fat_loss_plus_lean_mass_loss
          Extraction location
          Full text Table 1 formula and section 3.2
          • Fraction of combined fat and lean mass losses; not a skeletal-muscle fraction or an individual prediction.

          What the curated evidence supports

          • The DXA substudy analyzed 160 participants: 124 receiving pooled tirzepatide doses and 36 receiving placebo. At 72 weeks, changes in weight, fat and lean mass were −21.3%, −33.9% and −10.9% with tirzepatide, versus −5.3%, −8.2% and −2.6% with placebo.
          • In this analysis, DXA lean mass is fat-free mass minus bone mineral content. It includes tissues other than muscle and, alone, does not describe strength or diagnose sarcopenia.
          • The article describes roughly three quarters of combined fat and lean mass losses as fat. This sample-level composition does not justify saying that one quarter of lost weight was skeletal muscle.

          Limitations

          • 160 of 255 substudy enrollees were analyzed; 5, 10 and 15 mg doses were pooled.
          • DXA lean mass does not directly measure skeletal muscle or strength.
          • There was no multiplicity adjustment; missing data from three participants used last observation carried forward.

          Verification scope

          Verified through 2026-11-04 within the consulted scope.

          Bibliographic metadata checked
          Yes
          Original article abstract consulted
          Yes
          Full-text consultation
          Consulted
          Official trial registry consulted
          Yes
          Statistical analysis plan consulted
          No
          Verification boundary
          Verification is limited to the specific fields and sources consulted; it is not a full systematic appraisal or GRADE rating.

          Source record

          Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight (2025). Diabetes, obesity & metabolism.

          Source identifiers

          • Article DOI: 10.1111/dom.16275
          • PubMed record 39996356
          • PubMed Central: PMC11965027
          • Trial registration: NCT04184622
          • Structured registry: NCT04184622

          Controlled study

          SURMOUNT-1: weight change at 72 weeks

          In SURMOUNT-1, mean weight changes at 72 weeks were −15.0%, −19.5% and −20.9% with tirzepatide 5, 10 and 15 mg, and −3.1% with placebo, under the treatment-regimen estimand.

          The SURMOUNT-1 abstract reports adverse-event discontinuation in 4.3%, 7.1% and 6.2% of the 5, 10 and 15 mg groups, and 2.6% of the placebo group.

          Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Evidence design
          Randomized comparison
          Population
          Adults without diabetes with BMI >=30 kg/m2, or BMI >=27 kg/m2 with at least one weight-related complication.
          Assessment period
          Baseline to week 72; During the trial; precise safety window not verified
          Reported units
          % change; %

          Keep in view

          • These article results use the treatment-regimen estimand; current registry results include an analysis with a different discontinuation rule.
          • Arm sizes were verified by group titles, not by array position in the registry.
          See study details — SURMOUNT-1

          Study design and methods

          Randomized comparison

          Randomized, double-blind, placebo-controlled trial; four parallel groups allocated 1:1:1:1; 72 weeks; phase 3.

          Population

          Adults without diabetes with BMI >=30 kg/m2, or BMI >=27 kg/m2 with at least one weight-related complication.

          Outcome definition
          Percent change in body weight from baseline
          Assessment period
          Value
          72
          Unit
          weeks
          Reported statistic
          Mean
          Unit
          % change from baseline
          Randomized participants
          2539
          Estimand and analysis rules
          Name
          treatment-regimen estimand
          Definition
          Effects regardless of treatment discontinuation in the intention-to-treat population, according to the primary article abstract.
          Registry analysis distinction
          The current registry primary-outcome results specify data excluding observations after prematurely stopping study drug and use outcome-specific analyzed denominators. They must not be relabeled as the publication treatment-regimen values. Here, arm sample sizes are randomized counts from the participant-flow module, mapped by explicit group titles.

          Extracted outcomes

          Reported values, analysis populations and uncertainty, preserved from the curated extraction.
          Outcome and groupReported valueAssessment periodSample and denominatorsUncertainty
          Percent change in body weight

          Tirzepatide 5 mg

          Effect estimate

          		-15 % change

          Mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 630 — intention-to-treat population

          • 2539 — randomized total; scope: entire trial
          • 630 — randomized group; scope: tirzepatide 5mg

          95% confidence interval: -15.9 to -14.2

          Percent change in body weight

          Tirzepatide 10 mg

          Effect estimate

          		-19.5 % change

          Mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 636 — intention-to-treat population

          • 2539 — randomized total; scope: entire trial
          • 636 — randomized group; scope: tirzepatide 10mg

          95% confidence interval: -20.4 to -18.5

          Percent change in body weight

          Tirzepatide 15 mg

          Effect estimate

          		-20.9 % change

          Mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 630 — intention-to-treat population

          • 2539 — randomized total; scope: entire trial
          • 630 — randomized group; scope: tirzepatide 15mg

          95% confidence interval: -21.8 to -19.9

          Percent change in body weight

          Placebo

          Effect estimate

          		-3.1 % change

          Mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 643 — intention-to-treat population

          • 2539 — randomized total; scope: entire trial
          • 643 — randomized group; scope: Placebo

          95% confidence interval: -4.3 to -1.9

          Discontinuation due to adverse events

          Tirzepatide 5 mg weekly

          Descriptive result; not an effect estimate

          		4.3 %

          reported event percentage

          Unit: %

          		During the trial; precise safety window not verified

          Reported N: Not reported or not verified — outcome-specific denominator not verified

          • 630 — randomized arm context only; scope: tirzepatide 5mg

          Confidence interval for this event was not verified; descriptive count or percentage.

          Discontinuation due to adverse events

          Tirzepatide 10 mg weekly

          Descriptive result; not an effect estimate

          		7.1 %

          reported event percentage

          Unit: %

          		During the trial; precise safety window not verified

          Reported N: Not reported or not verified — outcome-specific denominator not verified

          • 636 — randomized arm context only; scope: tirzepatide 10mg

          Confidence interval for this event was not verified; descriptive count or percentage.

          Discontinuation due to adverse events

          Tirzepatide 15 mg weekly

          Descriptive result; not an effect estimate

          		6.2 %

          reported event percentage

          Unit: %

          		During the trial; precise safety window not verified

          Reported N: Not reported or not verified — outcome-specific denominator not verified

          • 630 — randomized arm context only; scope: tirzepatide 15mg

          Confidence interval for this event was not verified; descriptive count or percentage.

          Discontinuation due to adverse events

          Placebo

          Descriptive result; not an effect estimate

          		2.6 %

          reported event percentage

          Unit: %

          		During the trial; precise safety window not verified

          Reported N: Not reported or not verified — outcome-specific denominator not verified

          • 643 — randomized arm context only; scope: Placebo

          Confidence interval for this event was not verified; descriptive count or percentage.

          Percent change in body weight — Tirzepatide 5 mg: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          baseline_body_weight
          Estimand and analysis rules
          Name
          treatment-regimen estimand
          Definition
          Effects regardless of treatment discontinuation in the intention-to-treat population, according to the primary article abstract.
          Extraction location
          Original article abstract; arm sample sizes cross-checked against registry participant flow
          Percent change in body weight — Tirzepatide 10 mg: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          baseline_body_weight
          Estimand and analysis rules
          Name
          treatment-regimen estimand
          Definition
          Effects regardless of treatment discontinuation in the intention-to-treat population, according to the primary article abstract.
          Extraction location
          Original article abstract; arm sample sizes cross-checked against registry participant flow
          Percent change in body weight — Tirzepatide 15 mg: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          baseline_body_weight
          Estimand and analysis rules
          Name
          treatment-regimen estimand
          Definition
          Effects regardless of treatment discontinuation in the intention-to-treat population, according to the primary article abstract.
          Extraction location
          Original article abstract; arm sample sizes cross-checked against registry participant flow
          Percent change in body weight — Placebo: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          baseline_body_weight
          Estimand and analysis rules
          Name
          treatment-regimen estimand
          Definition
          Effects regardless of treatment discontinuation in the intention-to-treat population, according to the primary article abstract.
          Extraction location
          Original article abstract; arm sample sizes cross-checked against registry participant flow
          Discontinuation due to adverse events — Tirzepatide 5 mg weekly: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          Original article abstract, safety results
          • The safety denominator was not inferred from the randomized arm size.
          Discontinuation due to adverse events — Tirzepatide 10 mg weekly: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          Original article abstract, safety results
          • The safety denominator was not inferred from the randomized arm size.
          Discontinuation due to adverse events — Tirzepatide 15 mg weekly: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          Original article abstract, safety results
          • The safety denominator was not inferred from the randomized arm size.
          Discontinuation due to adverse events — Placebo: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          Original article abstract, safety results
          • The safety denominator was not inferred from the randomized arm size.

          What the curated evidence supports

          • In SURMOUNT-1, mean weight changes at 72 weeks were −15.0%, −19.5% and −20.9% with tirzepatide 5, 10 and 15 mg, and −3.1% with placebo, under the treatment-regimen estimand.
          • The SURMOUNT-1 abstract reports adverse-event discontinuation in 4.3%, 7.1% and 6.2% of the 5, 10 and 15 mg groups, and 2.6% of the placebo group.
          • Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Limitations

          • These article results use the treatment-regimen estimand; current registry results include an analysis with a different discontinuation rule.
          • Arm sizes were verified by group titles, not by array position in the registry.

          Verification scope

          Verified through 2026-11-04 within the consulted scope.

          Bibliographic metadata checked
          Yes
          Original article abstract consulted
          Yes
          Full-text consultation
          Not consulted
          Official trial registry consulted
          Yes
          Statistical analysis plan consulted
          No
          Verification boundary
          Verification is limited to the specific fields and sources consulted; it is not a full systematic appraisal or GRADE rating.

          Source record

          Tirzepatide Once Weekly for the Treatment of Obesity (2022). The New England journal of medicine.

          Source identifiers

          • Article DOI: 10.1056/NEJMoa2206038
          • PubMed record 35658024
          • Trial registration: NCT04184622
          • Structured registry: NCT04184622

          Controlled study

          SURMOUNT-4: continuation or withdrawal after a 36-week tirzepatide lead-in

          After a 36-week tirzepatide lead-in, 670 participants were randomized. Over the next 52 weeks, weight change from randomization was −5.5% with continued tirzepatide and +14.0% after switching to placebo; adjusted difference −19.4 percentage points (95% CI −21.2 to −17.7).

          During the SURMOUNT-4 randomized phase and safety follow-up, serious adverse events occurred in 10 of 335 participants in each group. Adverse-event discontinuation was 1.8% with continued tirzepatide and 0.9% with placebo.

          Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Evidence design
          Randomized withdrawal comparison
          Population
          Adults aged >=18 years with BMI >=30 kg/m2, or >=27 kg/m2 with a weight-related complication, without diabetes; randomized population had completed 36-week lead-in and achieved a tolerated tirzepatide dose of 10 or 15 mg. Lifestyle counseling continued in both randomized groups.
          Assessment period
          Randomization at week 36 to week 88; Weeks 36–88 and safety follow-up
          Reported units
          % change; percentage points; %

          Keep in view

          • The percentage reference is body weight at week 36, not initial week-zero weight.
          • The randomized population was selected after reaching a tolerated dose: 670 of 783 lead-in enrollees.
          • A 14% increase relative to week-36 weight does not mean regaining 14% of the weight previously lost.
          • This does not evaluate gradual tapering, other maintenance strategies or individual treatment decisions.
          See study details — SURMOUNT-4

          Study design and methods

          Randomized withdrawal comparison

          Phase 3 trial: 36-week open-label tirzepatide lead-in, followed by 52-week randomized 1:1 double-blind placebo-controlled withdrawal phase.

          Population

          Adults aged >=18 years with BMI >=30 kg/m2, or >=27 kg/m2 with a weight-related complication, without diabetes; randomized population had completed 36-week lead-in and achieved a tolerated tirzepatide dose of 10 or 15 mg. Lifestyle counseling continued in both randomized groups.

          Outcome definition
          Percent change in body weight from randomization at week 36 to week 88
          Assessment period
          Value
          52
          Unit
          weeks
          Starting study week
          36
          Ending study week
          88
          Time reference
          randomization after open-label lead-in
          Reported statistic
          least-squares mean
          Unit
          % change from randomization
          Open-label lead-in enrollees
          783
          Lead-in participants who received at least one dose
          782
          Randomized participants
          670
          Estimand and analysis rules
          Name
          treatment-regimen estimand
          Definition
          Mean treatment effect for all randomized participants regardless of adherence, using the full analysis set.
          Statistical analysis
          ANCOVA for continuous endpoints; Figure 2 describes hybrid imputation. Detailed imputation beyond the published Methods was not reverified from the supplement.
          Secondary estimand distinction
          Efficacy estimand excludes post-discontinuation data and uses MMRM. Registry values -6.7% versus +14.8% and difference -21.4 pp belong to this different analysis and are not mixed into this primary card.

          Extracted outcomes

          Reported values, analysis populations and uncertainty, preserved from the curated extraction.
          Outcome and groupReported valueAssessment periodSample and denominatorsUncertainty
          Percent change in weight from week 36 to week 88

          Continued tirzepatide

          Effect estimate

          		-5.5 % change

          least-squares mean

          Unit: % change

          		Randomization at week 36 to week 88

          Study weeks 36–88

          Reported N: 335 — randomized full analysis population

          • 783 — lead in enrolled; scope: open label phase
          • 782 — lead in received at least one dose; scope: open label phase
          • 670 — randomized total; scope: withdrawal phase
          • 335 — randomized full analysis arm; scope: continued tirzepatide

          95% confidence interval: -6.8 to -4.2

          Percent change in weight from week 36 to week 88

          Switch to placebo at week 36

          Effect estimate

          		14 % change

          least-squares mean

          Unit: % change

          		Randomization at week 36 to week 88

          Study weeks 36–88

          Reported N: 335 — randomized full analysis population

          • 783 — lead in enrolled; scope: open label phase
          • 782 — lead in received at least one dose; scope: open label phase
          • 670 — randomized total; scope: withdrawal phase
          • 335 — randomized full analysis arm; scope: switch to placebo

          95% confidence interval: 12.8 to 15.2

          Percent change in weight from week 36 to week 88

          Continue tirzepatide minus switch to placebo

          Effect estimate

          		-19.4 percentage points

          adjusted mean difference

          Unit: percentage points

          		Randomization at week 36 to week 88

          Study weeks 36–88

          Reported N: 670 — combined randomized full analysis population

          • 783 — lead in enrolled; scope: open label phase
          • 782 — lead in received at least one dose; scope: open label phase
          • 670 — randomized total; scope: withdrawal phase

          95% confidence interval: -21.2 to -17.7

          Reported p-value: <0.001 (Between-group comparison)

          Participants with a serious adverse event

          Continued tirzepatide

          Descriptive result; not an effect estimate

          		3 %

          reported event percentage

          Exact numerator: 10

          Unit: %

          		Weeks 36–88 and safety follow-up

          Reported N: 335 — safety analysis population

          • 335 — safety group; scope: continued tirzepatide

          Event-frequency confidence interval not verified.

          Participants with a serious adverse event

          Switch to placebo at week 36

          Descriptive result; not an effect estimate

          		3 %

          reported event percentage

          Exact numerator: 10

          Unit: %

          		Weeks 36–88 and safety follow-up

          Reported N: 335 — safety analysis population

          • 335 — safety group; scope: switch to placebo

          Event-frequency confidence interval not verified.

          Discontinuation due to adverse events

          Continued tirzepatide

          Descriptive result; not an effect estimate

          		1.8 %

          reported event percentage

          Exact numerator: 6

          Unit: %

          		Weeks 36–88 and safety follow-up

          Reported N: 335 — safety analysis population

          • 335 — safety group; scope: continued tirzepatide

          Event-frequency confidence interval not verified.

          Discontinuation due to adverse events

          Switch to placebo at week 36

          Descriptive result; not an effect estimate

          		0.9 %

          reported event percentage

          Exact numerator: 3

          Unit: %

          		Weeks 36–88 and safety follow-up

          Reported N: 335 — safety analysis population

          • 335 — safety group; scope: switch to placebo

          Event-frequency confidence interval not verified.

          Percent change in weight from week 36 to week 88 — Continued tirzepatide: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          week_36_body_weight
          Estimand and analysis rules
          Name
          treatment-regimen estimand
          Definition
          Mean treatment effect for all randomized participants regardless of adherence, using the full analysis set.
          Statistical analysis
          ANCOVA for continuous endpoints; Figure 2 describes hybrid imputation. Detailed imputation beyond the published Methods was not reverified from the supplement.
          Secondary estimand distinction
          Efficacy estimand excludes post-discontinuation data and uses MMRM. Registry values -6.7% versus +14.8% and difference -21.4 pp belong to this different analysis and are not mixed into this primary card.
          Extraction location
          JAMA Table 2 (treatment-regimen estimand)
          Percent change in weight from week 36 to week 88 — Switch to placebo at week 36: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          week_36_body_weight
          Estimand and analysis rules
          Name
          treatment-regimen estimand
          Definition
          Mean treatment effect for all randomized participants regardless of adherence, using the full analysis set.
          Statistical analysis
          ANCOVA for continuous endpoints; Figure 2 describes hybrid imputation. Detailed imputation beyond the published Methods was not reverified from the supplement.
          Secondary estimand distinction
          Efficacy estimand excludes post-discontinuation data and uses MMRM. Registry values -6.7% versus +14.8% and difference -21.4 pp belong to this different analysis and are not mixed into this primary card.
          Extraction location
          JAMA Table 2 (treatment-regimen estimand)
          Percent change in weight from week 36 to week 88 — Continue tirzepatide minus switch to placebo: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          difference_in_percent_change_from_week_36
          Estimand and analysis rules
          Name
          treatment-regimen estimand
          Definition
          Mean treatment effect for all randomized participants regardless of adherence, using the full analysis set.
          Statistical analysis
          ANCOVA for continuous endpoints; Figure 2 describes hybrid imputation. Detailed imputation beyond the published Methods was not reverified from the supplement.
          Secondary estimand distinction
          Efficacy estimand excludes post-discontinuation data and uses MMRM. Registry values -6.7% versus +14.8% and difference -21.4 pp belong to this different analysis and are not mixed into this primary card.
          Extraction location
          JAMA Table 2; reported adjusted contrast
          • Published difference −19.4 pp; do not replace it with −19.5 from rounded arm means.
          Participants with a serious adverse event — Continued tirzepatide: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          JAMA Table 3
          • Safety after lead-in selection; it does not describe everyone starting tirzepatide.
          Participants with a serious adverse event — Switch to placebo at week 36: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          JAMA Table 3
          • Safety after lead-in selection; it does not describe everyone starting tirzepatide.
          Discontinuation due to adverse events — Continued tirzepatide: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          JAMA Table 3
          • Safety after lead-in selection; it does not describe everyone starting tirzepatide.
          Discontinuation due to adverse events — Switch to placebo at week 36: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          JAMA Table 3
          • Safety after lead-in selection; it does not describe everyone starting tirzepatide.

          What the curated evidence supports

          • After a 36-week tirzepatide lead-in, 670 participants were randomized. Over the next 52 weeks, weight change from randomization was −5.5% with continued tirzepatide and +14.0% after switching to placebo; adjusted difference −19.4 percentage points (95% CI −21.2 to −17.7).
          • During the SURMOUNT-4 randomized phase and safety follow-up, serious adverse events occurred in 10 of 335 participants in each group. Adverse-event discontinuation was 1.8% with continued tirzepatide and 0.9% with placebo.
          • Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Limitations

          • The percentage reference is body weight at week 36, not initial week-zero weight.
          • The randomized population was selected after reaching a tolerated dose: 670 of 783 lead-in enrollees.
          • A 14% increase relative to week-36 weight does not mean regaining 14% of the weight previously lost.
          • This does not evaluate gradual tapering, other maintenance strategies or individual treatment decisions.

          Verification scope

          Verified through 2026-11-04 within the consulted scope.

          Bibliographic metadata checked
          Yes
          Original article abstract consulted
          Yes
          Full-text consultation
          Consulted
          Official trial registry consulted
          Yes
          Statistical analysis plan consulted
          No
          Verification boundary
          Verification is limited to the specific fields and sources consulted; it is not a full systematic appraisal or GRADE rating.

          Source record

          Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial (2024). JAMA.

          Source identifiers

          • Article DOI: 10.1001/jama.2023.24945
          • PubMed record 38078870
          • Source record: jamanetwork.com/journals/jama/fullarticle/2812936
          • PubMed Central: PMC10714284
          • Trial registration: NCT04660643
          • Structured registry: NCT04660643

          Controlled study

          SURMOUNT-5: weight change at 72 weeks

          In SURMOUNT-5, adjusted mean weight change at 72 weeks was −20.2% with tirzepatide and −13.7% with semaglutide; the reported difference was −6.5 percentage points (95% CI −8.1 to −4.9).

          SURMOUNT-5 had 751 randomized participants, 750 who received at least one dose and 636 evaluable participants in the registered primary outcome; these counts describe different sets.

          In the SURMOUNT-5 registry, 18 of 374 tirzepatide-treated participants and 13 of 376 semaglutide-treated participants had serious adverse events during the registered 72-week window.

          Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Evidence design
          Randomized comparison
          Population
          Adults aged at least 18 years with BMI >=30 kg/m2, or BMI >=27 kg/m2 with at least one weight-related comorbidity, without type 2 diabetes. Both arms received diet and physical-activity intervention.
          Assessment period
          Baseline to week 72
          Reported units
          percentage points; participants; % change

          Keep in view

          • Open-label trial in adults without type 2 diabetes; group averages do not predict an individual's response.
          • 751 randomized, 750 treated/mITT and 636 evaluable in the registered outcome are different denominators.
          • Verification used the original abstract, registry and SAP; the full NEJM article was not accessed.
          See study details — SURMOUNT-5

          Study design and methods

          Randomized comparison

          Randomized, open-label, active-controlled superiority trial; allocation 1:1; 72 weeks; phase 3b.

          Population

          Adults aged at least 18 years with BMI >=30 kg/m2, or BMI >=27 kg/m2 with at least one weight-related comorbidity, without type 2 diabetes. Both arms received diet and physical-activity intervention.

          Outcome definition
          Percent change in body weight from baseline to week 72
          Assessment period
          Value
          72
          Unit
          weeks
          Reported statistic
          least-squares mean
          Unit
          % change from baseline
          Randomized participants
          751
          Modified intention-to-treat participants
          750
          Estimand and analysis rules
          Name
          modified treatment-regimen estimand
          Primary estimand
          Yes
          Analysis population
          Modified intention-to-treat: all randomized participants exposed to at least one dose, analyzed as randomized. FAS contains treatment-period data from mITT with the exclusions below.
          Treatment discontinuation
          Included regardless of discontinuation for any reason.
          Other weight-management medication
          Included except nonstudy crossover to the randomized comparator drug.
          Nonstudy comparator crossover
          Data after nonstudy tirzepatide in the semaglutide arm or nonstudy semaglutide in the tirzepatide arm excluded; missing week-72 values after early discontinuation are addressed by within-arm multiple imputation using observed post-discontinuation outcomes.
          Bariatric or other weight-loss procedures
          Post-procedure data excluded; missing body weight imputed using the worst/highest pre-procedure value from baseline onward.
          Other missing data
          SAP says sporadic missing week-72 data for other reasons unrelated to early discontinuation or procedures are not imputed.
          Analysis method
          ANCOVA with treatment, sex, BMI category, baseline prediabetes and baseline body weight; Rubin combination for multiple imputations.
          Secondary estimand distinction
          Efficacy estimand assumes continuation of assigned treatment without other anti-obesity therapies and is analyzed with MMRM in EAS; do not attach that estimand to these primary estimates.
          Denominator distinctions
          751 randomized (375/376); 750 received >=1 dose (374/376). ClinicalTrials.gov separately reports 636 evaluable participants for this primary outcome (318/318), with LS means and SE 0.59 in each arm. The 636 registry outcome denominator is not the randomized or safety population. It must not replace 750 as the mITT/FAS parent population or imply a complete-case-only analysis. Study completers are separately 319/319.

          Extracted outcomes

          Reported values, analysis populations and uncertainty, preserved from the curated extraction.
          Outcome and groupReported valueAssessment periodSample and denominatorsUncertainty
          Percent change in body weight

          Tirzepatide

          Effect estimate

          		-20.2 % change

          least-squares mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 374 — modified intention-to-treat parent population

          • 751 — randomized total; scope: entire trial
          • 375 — randomized group; scope: Tirzepatide
          • 374 — received at least one dose; scope: Tirzepatide
          • 318 — registry outcome evaluable; scope: Tirzepatide

          95% confidence interval: -21.4 to -19.1

          Percent change in body weight

          Semaglutide

          Effect estimate

          		-13.7 % change

          least-squares mean

          Unit: % change

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 376 — modified intention-to-treat parent population

          • 751 — randomized total; scope: entire trial
          • 376 — randomized group; scope: Semaglutide
          • 376 — received at least one dose; scope: Semaglutide
          • 318 — registry outcome evaluable; scope: Semaglutide

          95% confidence interval: -14.9 to -12.6

          Percent change in body weight

          Tirzepatide minus semaglutide

          Effect estimate

          		-6.5 percentage points

          adjusted mean difference

          Unit: percentage points

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 750 — combined modified intention-to-treat parent population

          • 751 — randomized total; scope: entire trial
          • 750 — modified intention-to-treat total; scope: entire trial
          • 636 — registry outcome-evaluable total; scope: primary registry outcome

          95% confidence interval: -8.1 to -4.9

          Reported p-value: <0.001 (Between-group comparison)

          Participants with a serious adverse event

          Tirzepatide

          Descriptive result; not an effect estimate

          		18 participants

          event count

          Exact numerator: 18

          Unit: participants

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 374 — safety analysis population

          • 374 — safety group; scope: Tirzepatide

          Confidence interval for this event was not verified; descriptive count or percentage.

          Participants with a serious adverse event

          Semaglutide

          Descriptive result; not an effect estimate

          		13 participants

          event count

          Exact numerator: 13

          Unit: participants

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 376 — safety analysis population

          • 376 — safety group; scope: Semaglutide

          Confidence interval for this event was not verified; descriptive count or percentage.

          Deaths

          Tirzepatide

          Descriptive result; not an effect estimate

          		0 participants

          event count

          Exact numerator: 0

          Unit: participants

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 374 — safety analysis population

          • 374 — safety group; scope: Tirzepatide

          Confidence interval for this event was not verified; descriptive count or percentage.

          Deaths

          Semaglutide

          Descriptive result; not an effect estimate

          		0 participants

          event count

          Exact numerator: 0

          Unit: participants

          		Baseline to week 72

          Study weeks 0–72

          Reported N: 376 — safety analysis population

          • 376 — safety group; scope: Semaglutide

          Confidence interval for this event was not verified; descriptive count or percentage.

          Percent change in body weight — Tirzepatide: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          baseline_body_weight
          Estimand and analysis rules
          Name
          modified treatment-regimen estimand
          Primary estimand
          Yes
          Analysis population
          Modified intention-to-treat: all randomized participants exposed to at least one dose, analyzed as randomized. FAS contains treatment-period data from mITT with the exclusions below.
          Treatment discontinuation
          Included regardless of discontinuation for any reason.
          Other weight-management medication
          Included except nonstudy crossover to the randomized comparator drug.
          Nonstudy comparator crossover
          Data after nonstudy tirzepatide in the semaglutide arm or nonstudy semaglutide in the tirzepatide arm excluded; missing week-72 values after early discontinuation are addressed by within-arm multiple imputation using observed post-discontinuation outcomes.
          Bariatric or other weight-loss procedures
          Post-procedure data excluded; missing body weight imputed using the worst/highest pre-procedure value from baseline onward.
          Other missing data
          SAP says sporadic missing week-72 data for other reasons unrelated to early discontinuation or procedures are not imputed.
          Analysis method
          ANCOVA with treatment, sex, BMI category, baseline prediabetes and baseline body weight; Rubin combination for multiple imputations.
          Secondary estimand distinction
          Efficacy estimand assumes continuation of assigned treatment without other anti-obesity therapies and is analyzed with MMRM in EAS; do not attach that estimand to these primary estimates.
          Extraction location
          Original article abstract; arm sample sizes cross-checked against registry participant flow
          Percent change in body weight — Semaglutide: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          baseline_body_weight
          Estimand and analysis rules
          Name
          modified treatment-regimen estimand
          Primary estimand
          Yes
          Analysis population
          Modified intention-to-treat: all randomized participants exposed to at least one dose, analyzed as randomized. FAS contains treatment-period data from mITT with the exclusions below.
          Treatment discontinuation
          Included regardless of discontinuation for any reason.
          Other weight-management medication
          Included except nonstudy crossover to the randomized comparator drug.
          Nonstudy comparator crossover
          Data after nonstudy tirzepatide in the semaglutide arm or nonstudy semaglutide in the tirzepatide arm excluded; missing week-72 values after early discontinuation are addressed by within-arm multiple imputation using observed post-discontinuation outcomes.
          Bariatric or other weight-loss procedures
          Post-procedure data excluded; missing body weight imputed using the worst/highest pre-procedure value from baseline onward.
          Other missing data
          SAP says sporadic missing week-72 data for other reasons unrelated to early discontinuation or procedures are not imputed.
          Analysis method
          ANCOVA with treatment, sex, BMI category, baseline prediabetes and baseline body weight; Rubin combination for multiple imputations.
          Secondary estimand distinction
          Efficacy estimand assumes continuation of assigned treatment without other anti-obesity therapies and is analyzed with MMRM in EAS; do not attach that estimand to these primary estimates.
          Extraction location
          Original article abstract; arm sample sizes cross-checked against registry participant flow
          Percent change in body weight — Tirzepatide minus semaglutide: extraction context
          Outcome role
          Not specified in the consulted scope
          Scale reference
          Difference in percent change
          Estimand and analysis rules
          Name
          modified treatment-regimen estimand
          Primary estimand
          Yes
          Analysis population
          Modified intention-to-treat: all randomized participants exposed to at least one dose, analyzed as randomized. FAS contains treatment-period data from mITT with the exclusions below.
          Treatment discontinuation
          Included regardless of discontinuation for any reason.
          Other weight-management medication
          Included except nonstudy crossover to the randomized comparator drug.
          Nonstudy comparator crossover
          Data after nonstudy tirzepatide in the semaglutide arm or nonstudy semaglutide in the tirzepatide arm excluded; missing week-72 values after early discontinuation are addressed by within-arm multiple imputation using observed post-discontinuation outcomes.
          Bariatric or other weight-loss procedures
          Post-procedure data excluded; missing body weight imputed using the worst/highest pre-procedure value from baseline onward.
          Other missing data
          SAP says sporadic missing week-72 data for other reasons unrelated to early discontinuation or procedures are not imputed.
          Analysis method
          ANCOVA with treatment, sex, BMI category, baseline prediabetes and baseline body weight; Rubin combination for multiple imputations.
          Secondary estimand distinction
          Efficacy estimand assumes continuation of assigned treatment without other anti-obesity therapies and is analyzed with MMRM in EAS; do not attach that estimand to these primary estimates.
          Extraction location
          Published comparison; SURMOUNT-5 contrast CI verified in official registry
          • Reported difference; not recomputed from rounded arm means.
          Participants with a serious adverse event — Tirzepatide: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          ClinicalTrials.gov adverseEventsModule.eventGroups; baseline through week 72
          • Descriptive safety result; no inference of comparative safety superiority.
          Participants with a serious adverse event — Semaglutide: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          ClinicalTrials.gov adverseEventsModule.eventGroups; baseline through week 72
          • Descriptive safety result; no inference of comparative safety superiority.
          Deaths — Tirzepatide: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          ClinicalTrials.gov adverseEventsModule.eventGroups; baseline through week 72
          • Descriptive safety result; no inference of comparative safety superiority.
          Deaths — Semaglutide: extraction context
          Outcome role
          Descriptive safety outcome
          Extraction location
          ClinicalTrials.gov adverseEventsModule.eventGroups; baseline through week 72
          • Descriptive safety result; no inference of comparative safety superiority.

          What the curated evidence supports

          • In SURMOUNT-5, adjusted mean weight change at 72 weeks was −20.2% with tirzepatide and −13.7% with semaglutide; the reported difference was −6.5 percentage points (95% CI −8.1 to −4.9).
          • SURMOUNT-5 had 751 randomized participants, 750 who received at least one dose and 636 evaluable participants in the registered primary outcome; these counts describe different sets.
          • In the SURMOUNT-5 registry, 18 of 374 tirzepatide-treated participants and 13 of 376 semaglutide-treated participants had serious adverse events during the registered 72-week window.
          • Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.

          Limitations

          • Open-label trial in adults without type 2 diabetes; group averages do not predict an individual's response.
          • 751 randomized, 750 treated/mITT and 636 evaluable in the registered outcome are different denominators.
          • Verification used the original abstract, registry and SAP; the full NEJM article was not accessed.

          Verification scope

          Verified through 2026-11-04 within the consulted scope.

          Bibliographic metadata checked
          Yes
          Original article abstract consulted
          Yes
          Full-text consultation
          Not consulted
          Official trial registry consulted
          Yes
          Statistical analysis plan consulted
          Yes
          Verification boundary
          Verification is limited to the specific fields and sources consulted; it is not a full systematic appraisal or GRADE rating.

          Source record

          Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (2025). The New England journal of medicine.

          Source identifiers

          • Article DOI: 10.1056/NEJMoa2416394
          • PubMed record 40353578
          • Trial registration: NCT05822830
          • Structured registry: NCT05822830
          • Statistical analysis plan: NCT05822830 · SAP_001.pdf