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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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.