Journey | nuViteo

OVERVIEW + STUDY DETAILS

Follow the evidence.

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

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 and methods: Original extraction in Portuguese is available in the study details.
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

Original extraction (Portuguese)

População

Adultos de 21–40 anos, IMC 25,0–29,9 kg/m² e sono habitual inferior a 6,5 h/noite.

Study design: Ensaio randomizado de centro único; duas semanas basais e duas semanas de intervenção em ambiente habitual; análise por intenção de tratar.
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: Ampliar o sono reduz ingestão energética objetivamente estimada em adultos com sobrepeso e sono curto?
Qualified findings: O aconselhamento para estender o sono aumentou sua duração e reduziu a ingestão estimada frente ao controle. O gasto total não diferiu significativamente. O resultado é de duas semanas; não demonstra manutenção do emagrecimento.
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 group	Reported value	Assessment period	Sample and denominators	Uncertainty
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)

Read the original sources

Controlled study

STEP 1: weight change at 68 weeks

STEP 1 • NCT03548935

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.

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 group	Reported value	Assessment period	Sample and denominators	Uncertainty
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.

Read the original sources

Controlled study

SURMOUNT-1: weight change at 72 weeks

SURMOUNT-1 • NCT04184622

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.

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 group	Reported value	Assessment period	Sample and denominators	Uncertainty
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.

Read the original sources

Controlled study

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

SURMOUNT-4 • NCT04660643

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.

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 group	Reported value	Assessment period	Sample and denominators	Uncertainty
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.

Read the original sources

Controlled study

SURMOUNT-5: weight change at 72 weeks

SURMOUNT-5 • NCT05822830

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.

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 group	Reported value	Assessment period	Sample and denominators	Uncertainty
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.

Read the original sources

THE RESEARCH LANDSCAPE

Explore the research landscape

See the scale of the consolidated catalog, the prioritized registry cohort, and the smaller set of evidence cards published in this release.

46,042

Consolidated research records

112,151

Mapped files

Scientific catalog areas

Explore all 16 scientific areas

Clinical obesity and overweight14,981

GLP-1, GIP and incretin medicines2,081

Insulin resistance and glycemic health6,298

Calorie deficit and energy balance580

Thermogenesis and energy expenditure461

Fat oxidation and ketosis74

Intermittent fasting and chrononutrition621

Nutrition, eating and satiety5,932

Muscle preservation and body composition3,735

Gut microbiome and metabolomics607

Physical activity and exercise3,696

Sleep, stress and eating behavior1,358

Weight maintenance and regain164

Bariatric and metabolic surgery2,383

Digital technologies and remote interventions585

Cardiovascular, liver and inflammatory outcomes2,486

Catalog identities consolidate DOI, NCT, PMID, PMCID and normalized titles; the count is not a certified count of independent peer-reviewed publications.

Prioritized clinical registry records

570 records

Weight as a primary outcome: 342
BMI as a primary outcome: 112
Adiposity or waist as a primary outcome: 49
Weight-related outcomes only as secondary outcomes: 29
No direct weight-related outcome identified: 38

Each record has one principal outcome class. This classification does not mean that a trial has only one outcome or that its findings have passed full scientific appraisal.

PUBLISHED CURATED EVIDENCE

13evidence cards

Directed selection of sources and claims verified within the fields and sections actually consulted.

60 result records23 reviewed claims

Search covers these 13 published evidence cards.

Catalog size and metadata completeness do not grade scientific certainty. The 570-record panorama describes a prioritized registry cohort, not 570 publicly reviewed evidence cards.

THE INAUGURAL BRIEFING

Video in preparation

Muscle, Strength & Weight Loss: What Does DXA Measure?

Planned inaugural nuViteo YouTube briefing on DXA lean mass, skeletal muscle, and strength, using the same SURMOUNT-1 substudy and EWGSOP2 evidence as the conceptual guide sample.

Read the briefing outline

OVERVIEW + STUDY DETAILS

Sources supporting the briefing.

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

Conceptual consensus

EWGSOP2: sarcopenia definition and assessment

EWGSOP2 • PMID 30312372

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.

Read the original sources

Controlled study

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

SURMOUNT-1 DXA • NCT04184622

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 group	Reported value	Assessment period	Sample and denominators	Uncertainty
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.