{ "name": "The RX Index GLP-1 Lean-Mass Evidence Map", "alternate_name": "RXI GLP-1 Lean-Mass Evidence Map v1.0", "dataset_version": "1.0", "verified_date": "2026-08-01", "publisher": "The RX Index", "creator": "The RX Index Editorial Team", "canonical_page": "https://therxindex.com/research/glp1-lean-mass-by-drug/", "description": "A versioned primary-source evidence map of obesity-drug body-composition findings, with study population, dose, duration, method, body region, estimand, provenance and comparability limits.", "central_finding": "No randomized head-to-head body-composition trial of approved obesity products establishes which preserves the most lean tissue.", "methodology": { "scope": "Randomized adult obesity evidence for current U.S. chronic-weight-management ingredients with GLP-1 activity, with regional, diabetes-only, investigational, single-arm and observational evidence kept in separate tiers.", "calculation": "Lean share of measured tissue loss = absolute lean mass loss / (absolute fat mass loss + absolute lean mass loss) x 100.", "calculation_gate": [ "same analyzed participants", "same estimand or missing-data framework", "same timepoint", "same treatment group", "same body region" ], "provenance_codes": { "DR-WB": "Investigators directly reported a whole-body share.", "DR-R": "Investigators directly reported, or supplied compatible inputs for, a regional share.", "RXI-CALC": "The RX Index calculated the value from compatible primary-source inputs.", "NR": "The source did not report an equivalent result.", "NQL": "No qualifying result was located under the stated protocol as of the verification date." }, "interpretation_limit": "Adjacent rows are not a statistical head-to-head comparison. DXA lean mass is not synonymous with skeletal muscle." }, "row_count": 19, "variables": [ "dataset_version", "verified_date", "evidence_tier", "active_ingredient_or_regimen", "product_context", "regulatory_status", "study", "study_design", "population", "parent_trial_n", "body_composition_n", "treatment_n", "comparator_n", "dose", "duration_weeks", "method", "body_region", "estimand", "body_weight_change", "fat_change", "lean_change", "fat_share_pct", "lean_share_pct", "metric_provenance", "functional_result", "comparability_notes", "publish_status", "source_url" ], "data": [ { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Core approved-drug obesity evidence", "active_ingredient_or_regimen": "Semaglutide", "product_context": "Wegovy injection", "regulatory_status": "FDA-approved", "study": "STEP 1 DXA substudy — treatment-policy estimand", "study_design": "Randomized placebo-controlled obesity trial substudy", "population": "Adults with overweight or obesity without diabetes", "parent_trial_n": 1961, "body_composition_n": 140, "treatment_n": 95, "comparator_n": 45, "dose": "2.4 mg once weekly", "duration_weeks": 68, "method": "DXA", "body_region": "Whole body", "estimand": "Treatment-policy estimand", "body_weight_change": "Not used in share calculation", "fat_change": "-8.36 kg", "lean_change": "-5.26 kg", "fat_share_pct": 61.4, "lean_share_pct": 38.6, "metric_provenance": "RXI-CALC", "functional_result": "Not a muscle-function endpoint", "comparability_notes": "Share uses measured fat plus lean tissue loss in the same 95-person treatment group and estimand; denominator is not scale-weight loss; DXA lean mass is not skeletal muscle.", "publish_status": "Publish with denominator label", "source_url": "https://cci-cic.org/wp-content/uploads/2021/04/STEP-Appendix.pdf" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Core approved-drug obesity evidence", "active_ingredient_or_regimen": "Semaglutide", "product_context": "Wegovy injection", "regulatory_status": "FDA-approved", "study": "STEP 1 DXA substudy — trial-product estimand", "study_design": "Randomized placebo-controlled obesity trial substudy", "population": "Adults with overweight or obesity without diabetes", "parent_trial_n": 1961, "body_composition_n": 140, "treatment_n": 95, "comparator_n": 45, "dose": "2.4 mg once weekly", "duration_weeks": 68, "method": "DXA", "body_region": "Whole body", "estimand": "Trial-product estimand", "body_weight_change": "Not used in share calculation", "fat_change": "-10.40 kg", "lean_change": "-6.92 kg", "fat_share_pct": 60.0, "lean_share_pct": 40.0, "metric_provenance": "RXI-CALC", "functional_result": "Not a muscle-function endpoint", "comparability_notes": "Share uses measured fat plus lean tissue loss in the same 95-person treatment group and estimand; denominator is not scale-weight loss; DXA lean mass is not skeletal muscle.", "publish_status": "Publish with denominator label", "source_url": "https://cci-cic.org/wp-content/uploads/2021/04/STEP-Appendix.pdf" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Core approved-drug obesity evidence", "active_ingredient_or_regimen": "Tirzepatide", "product_context": "Zepbound", "regulatory_status": "FDA-approved", "study": "SURMOUNT-1 DXA substudy", "study_design": "Randomized placebo-controlled obesity trial substudy", "population": "Adults with overweight or obesity without diabetes", "parent_trial_n": 2539, "body_composition_n": 160, "treatment_n": 124, "comparator_n": 36, "dose": "Pooled 5, 10 and 15 mg once weekly", "duration_weeks": 72, "method": "DXA", "body_region": "Whole body", "estimand": "Paired baseline and week-72 DXA analysis", "body_weight_change": "-21.3%", "fat_change": "-33.9%", "lean_change": "-10.9%; mean absolute lean loss -5.6 kg", "fat_share_pct": 75.0, "lean_share_pct": 25.0, "metric_provenance": "DR-WB", "functional_result": "No qualifying objective function endpoint in the body-composition report", "comparability_notes": "Direct whole-body share, but pooled across all three maintenance doses; not dose-specific. Published correction changes a figure y-axis unit, not the table values used here.", "publish_status": "Publish", "source_url": "https://doi.org/10.1111/dom.16275" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Core approved-drug obesity evidence", "active_ingredient_or_regimen": "Orforglipron", "product_context": "Foundayo", "regulatory_status": "FDA-approved", "study": "ATTAIN-1 DXA subgroup", "study_design": "Randomized placebo-controlled obesity trial subgroup", "population": "Adults with obesity without diabetes", "parent_trial_n": 3127, "body_composition_n": 171, "treatment_n": "", "comparator_n": "", "dose": "Pooled 6, 12 and 36 mg publication groups", "duration_weeks": 72, "method": "DXA", "body_region": "Whole body", "estimand": "Pooled body-composition analysis", "body_weight_change": "Dose-specific main-trial results; not used for pooled share", "fat_change": "-13.8%", "lean_change": "-4.5%", "fat_share_pct": 73.1, "lean_share_pct": 26.9, "metric_provenance": "DR-WB", "functional_result": "No qualifying objective function endpoint in the extracted subgroup result", "comparability_notes": "Direct whole-body pooled-dose result. Publication-dose numbers are not treated as interchangeable with current marketed Foundayo strengths.", "publish_status": "Publish", "source_url": "https://doi.org/10.1056/NEJMoa2511774" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Core approved-drug obesity evidence", "active_ingredient_or_regimen": "Liraglutide", "product_context": "Saxenda", "regulatory_status": "FDA-approved", "study": "Randomized 20-week obesity study", "study_design": "Randomized double-blind placebo- and active-controlled obesity trial", "population": "Adults with obesity without diabetes", "parent_trial_n": 564, "body_composition_n": "Not stated for the 3.0 mg result in the published abstract", "treatment_n": "", "comparator_n": "", "dose": "3.0 mg once daily", "duration_weeks": 20, "method": "DXA/CT body-composition substudy", "body_region": "Body composition and abdominal fat", "estimand": "Published 20-week result", "body_weight_change": "", "fat_change": "-15.4%", "lean_change": "-2.0%", "fat_share_pct": "", "lean_share_pct": "", "metric_provenance": "NR", "functional_result": "No qualifying objective function endpoint in the extracted result", "comparability_notes": "Separate fat and lean changes are reported, but no equivalent dose-specific lean share is available from the cited result.", "publish_status": "Publish without share", "source_url": "https://pubmed.ncbi.nlm.nih.gov/21844879/" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Same-protocol investigational comparison", "active_ingredient_or_regimen": "Cagrilintide 2.4 mg + semaglutide 2.4 mg", "product_context": "CagriSema", "regulatory_status": "Investigational", "study": "REDEFINE 1 DXA analysis", "study_design": "Randomized active- and placebo-controlled obesity trial; congress-reported body-composition analysis", "population": "Adults with overweight or obesity without diabetes", "parent_trial_n": 3417, "body_composition_n": 252, "treatment_n": "", "comparator_n": "", "dose": "2.4 mg/2.4 mg once weekly", "duration_weeks": 68, "method": "DXA", "body_region": "Whole body", "estimand": "Trial-product estimand", "body_weight_change": "-23.9%", "fat_change": "Fat share 66.9%", "lean_change": "Lean-soft-tissue share 33.1%", "fat_share_pct": 66.9, "lean_share_pct": 33.1, "metric_provenance": "DR-WB", "functional_result": "Sit-to-stand +2.5 repetitions vs +2.4 placebo; ETD 0.03 (95% CI -0.7 to 0.8), not significant; patient-reported function improved more.", "comparability_notes": "Same protocol as active semaglutide and cagrilintide arms, but body-composition detail is congress-reported and no pairwise inferential tests of lean shares are shown.", "publish_status": "Publish in separate investigational table", "source_url": "https://sciencehub.novonordisk.com/content/dam/sciencehub/global/en/congresses-and-scientific-publications/congresses/eco2026/ravussin/documents/eric-ravussin-redefine-1-body-comp-new-12may26.pdf" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Same-protocol investigational comparison", "active_ingredient_or_regimen": "Semaglutide", "product_context": "REDEFINE 1 active comparator", "regulatory_status": "Ingredient and 2.4 mg dose context FDA-approved", "study": "REDEFINE 1 DXA analysis", "study_design": "Randomized active- and placebo-controlled obesity trial; congress-reported body-composition analysis", "population": "Adults with overweight or obesity without diabetes", "parent_trial_n": 3417, "body_composition_n": 252, "treatment_n": "", "comparator_n": "", "dose": "2.4 mg once weekly", "duration_weeks": 68, "method": "DXA", "body_region": "Whole body", "estimand": "Trial-product estimand", "body_weight_change": "-16.6%", "fat_change": "Fat share 69.7%", "lean_change": "Lean-soft-tissue share 30.3%", "fat_share_pct": 69.7, "lean_share_pct": 30.3, "metric_provenance": "DR-WB", "functional_result": "Not separately reported in the cited presentation", "comparability_notes": "Same-protocol active arm; congress-reported body-composition analysis; no pairwise inferential test of lean share shown.", "publish_status": "Publish in separate same-protocol table", "source_url": "https://sciencehub.novonordisk.com/content/dam/sciencehub/global/en/congresses-and-scientific-publications/congresses/eco2026/ravussin/documents/eric-ravussin-redefine-1-body-comp-new-12may26.pdf" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Same-protocol investigational comparison", "active_ingredient_or_regimen": "Cagrilintide", "product_context": "REDEFINE 1 active comparator", "regulatory_status": "Investigational", "study": "REDEFINE 1 DXA analysis", "study_design": "Randomized active- and placebo-controlled obesity trial; congress-reported body-composition analysis", "population": "Adults with overweight or obesity without diabetes", "parent_trial_n": 3417, "body_composition_n": 252, "treatment_n": "", "comparator_n": "", "dose": "2.4 mg once weekly", "duration_weeks": 68, "method": "DXA", "body_region": "Whole body", "estimand": "Trial-product estimand", "body_weight_change": "-15.0%", "fat_change": "Fat share 62.9%", "lean_change": "Lean-soft-tissue share 37.1%", "fat_share_pct": 62.9, "lean_share_pct": 37.1, "metric_provenance": "DR-WB", "functional_result": "Not separately reported in the cited presentation", "comparability_notes": "Same-protocol active arm; congress-reported body-composition analysis; no pairwise inferential test of lean share shown.", "publish_status": "Publish in separate investigational table", "source_url": "https://sciencehub.novonordisk.com/content/dam/sciencehub/global/en/congresses-and-scientific-publications/congresses/eco2026/ravussin/documents/eric-ravussin-redefine-1-body-comp-new-12may26.pdf" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Same-protocol control", "active_ingredient_or_regimen": "Placebo", "product_context": "REDEFINE 1 control", "regulatory_status": "Control", "study": "REDEFINE 1 DXA analysis", "study_design": "Randomized active- and placebo-controlled obesity trial; congress-reported body-composition analysis", "population": "Adults with overweight or obesity without diabetes", "parent_trial_n": 3417, "body_composition_n": 252, "treatment_n": "", "comparator_n": "", "dose": "Placebo", "duration_weeks": 68, "method": "DXA", "body_region": "Whole body", "estimand": "Trial-product estimand", "body_weight_change": "-2.8%", "fat_change": "Fat share 56.7%", "lean_change": "Lean-soft-tissue share 43.3%", "fat_share_pct": 56.7, "lean_share_pct": 43.3, "metric_provenance": "DR-WB", "functional_result": "Sit-to-stand +2.4 repetitions", "comparability_notes": "Control arm from the same congress-reported analysis.", "publish_status": "Publish in separate same-protocol table", "source_url": "https://sciencehub.novonordisk.com/content/dam/sciencehub/global/en/congresses-and-scientific-publications/congresses/eco2026/ravussin/documents/eric-ravussin-redefine-1-body-comp-new-12may26.pdf" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Regional supporting evidence", "active_ingredient_or_regimen": "Semaglutide", "product_context": "Wegovy / Wegovy HD dose context", "regulatory_status": "Both doses FDA-approved; analysis pooled", "study": "STEP UP MRI analysis", "study_design": "Randomized placebo-controlled obesity trial regional MRI subgroup; congress presentation", "population": "Adults with obesity without diabetes", "parent_trial_n": "", "body_composition_n": 55, "treatment_n": 49, "comparator_n": 6, "dose": "Pooled 2.4 and 7.2 mg once weekly", "duration_weeks": 72, "method": "MRI with volume-to-mass conversion", "body_region": "Thoracic vertebra 9 to knees", "estimand": "Treatment-policy / in-trial regional analysis as presented", "body_weight_change": "-17.4% in pooled MRI subset", "fat_change": "-25.1%; -11.0 L", "lean_change": "-6.8%; -1.7 L", "fat_share_pct": 84.4, "lean_share_pct": 15.6, "metric_provenance": "DR-R", "functional_result": "Proximal muscle function assessed; regional result kept separate from total-body evidence", "comparability_notes": "Regional, not whole body; doses pooled; only six placebo participants; congress analysis.", "publish_status": "Publish in regional supporting table", "source_url": "https://sciencehub.novonordisk.com/content/dam/sciencehub/global/en/congresses-and-scientific-publications/congresses/easd2025/hjelmesaeth/documents/Hjelmes%C3%A6th_EASD25_STEP-UP_Body-Composition_Oral_Final_2025-09-25.pdf" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Diabetes supporting evidence", "active_ingredient_or_regimen": "Semaglutide", "product_context": "Ozempic diabetes-dose context", "regulatory_status": "FDA-approved for diabetes; not an obesity-dose result", "study": "SUSTAIN 8 body-composition substudy", "study_design": "Randomized double-blind active-controlled type 2 diabetes trial substudy", "population": "Adults with uncontrolled type 2 diabetes on metformin", "parent_trial_n": 788, "body_composition_n": 178, "treatment_n": 53, "comparator_n": 61, "dose": "1.0 mg once weekly", "duration_weeks": 52, "method": "DXA", "body_region": "Whole body", "estimand": "Observed end-of-treatment without rescue medication", "body_weight_change": "", "fat_change": "-3.4 kg", "lean_change": "-2.3 kg", "fat_share_pct": 59.6, "lean_share_pct": 40.4, "metric_provenance": "RXI-CALC", "functional_result": "No qualifying objective function endpoint", "comparability_notes": "Type 2 diabetes population, diabetes dose, active non-GLP-1 comparator, no placebo. Between-group body-composition changes were not significantly different.", "publish_status": "Publish in supporting table", "source_url": "https://doi.org/10.1007/s00125-019-05065-8" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Non-GLP-1 active control", "active_ingredient_or_regimen": "Canagliflozin", "product_context": "SUSTAIN 8 active control", "regulatory_status": "FDA-approved SGLT2 inhibitor", "study": "SUSTAIN 8 body-composition substudy", "study_design": "Randomized double-blind active-controlled type 2 diabetes trial substudy", "population": "Adults with uncontrolled type 2 diabetes on metformin", "parent_trial_n": 788, "body_composition_n": 178, "treatment_n": 61, "comparator_n": 53, "dose": "300 mg once daily", "duration_weeks": 52, "method": "DXA", "body_region": "Whole body", "estimand": "Observed end-of-treatment without rescue medication", "body_weight_change": "", "fat_change": "-2.6 kg", "lean_change": "-1.5 kg", "fat_share_pct": 63.4, "lean_share_pct": 36.6, "metric_provenance": "RXI-CALC", "functional_result": "No qualifying objective function endpoint", "comparability_notes": "Non-GLP-1 active control. Between-group body-composition changes were not significantly different.", "publish_status": "Publish in supporting table", "source_url": "https://doi.org/10.1007/s00125-019-05065-8" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Investigational diabetes supporting evidence", "active_ingredient_or_regimen": "Retatrutide", "product_context": "Investigational triple agonist", "regulatory_status": "Investigational; not FDA-approved", "study": "Phase 2 type 2 diabetes DXA substudy", "study_design": "Randomized phase 2 type 2 diabetes trial substudy", "population": "Adults with type 2 diabetes", "parent_trial_n": "", "body_composition_n": 103, "treatment_n": "", "comparator_n": "", "dose": "Pooled 4, 8 and 12 mg once weekly", "duration_weeks": 36, "method": "DXA", "body_region": "Whole body", "estimand": "End-of-treatment pooled effective-dose analysis", "body_weight_change": "", "fat_change": "Reported fat-loss index 64.6%", "lean_change": "Complement 35.4%", "fat_share_pct": 64.6, "lean_share_pct": 35.4, "metric_provenance": "RXI-CALC from reported fat-loss index complement", "functional_result": "No qualifying objective function endpoint", "comparability_notes": "Investigational, pooled doses, 36 weeks and type 2 diabetes population; not a current obesity-product result.", "publish_status": "Publish in supporting table", "source_url": "https://doi.org/10.1016/S2213-8587(25)00092-0" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Congress-only obesity supporting evidence", "active_ingredient_or_regimen": "Semaglutide", "product_context": "Wegovy injection context", "regulatory_status": "FDA-approved ingredient and dose context", "study": "STEP 12 Taiwan body-composition subset", "study_design": "Randomized obesity trial subset; congress abstract", "population": "Chinese adults with overweight or obesity; Taiwan subset", "parent_trial_n": "", "body_composition_n": 45, "treatment_n": "", "comparator_n": "", "dose": "2.4 mg once weekly", "duration_weeks": 44, "method": "Body-composition analysis", "body_region": "Not fully specified in accessible abstract", "estimand": "Accessible congress abstract", "body_weight_change": "", "fat_change": "Total-fat-mass proportion -6.2 percentage points", "lean_change": "Lean-body-mass proportion +5.7 percentage points", "fat_share_pct": "", "lean_share_pct": "", "metric_provenance": "NR", "functional_result": "Not reported in accessible abstract", "comparability_notes": "Accessible primary abstract does not report compatible absolute fat and lean losses; no share calculated.", "publish_status": "Publish without share in supporting table", "source_url": "https://doi.org/10.1002/oby.70102" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Prospective single-arm function context", "active_ingredient_or_regimen": "Semaglutide", "product_context": "Wegovy injection context", "regulatory_status": "FDA-approved ingredient and dose context", "study": "SEMALEAN", "study_design": "Prospective single-arm study", "population": "Adults treated with semaglutide 2.4 mg", "parent_trial_n": 115, "body_composition_n": 106, "treatment_n": 106, "comparator_n": "", "dose": "2.4 mg once weekly", "duration_weeks": 52, "method": "Body composition plus handgrip strength", "body_region": "Whole body / clinical assessment", "estimand": "Observed prospective follow-up", "body_weight_change": "-10% at month 7; -13% at month 12", "fat_change": "-14% at month 7; -18% at month 12", "lean_change": "-3 kg at month 7, then stable", "fat_share_pct": "", "lean_share_pct": "", "metric_provenance": "NR", "functional_result": "Handgrip strength +4.5 kg at month 12; sarcopenic-obesity prevalence 49% to 33%", "comparability_notes": "Single-arm design cannot establish a causal drug effect or comparative ranking.", "publish_status": "Publish in function context only", "source_url": "https://doi.org/10.1111/dom.70141" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Investigational body-composition modification evidence", "active_ingredient_or_regimen": "Bimagrumab", "product_context": "BELIEVE phase 2", "regulatory_status": "Investigational intravenous agent", "study": "BELIEVE week-72 analysis", "study_design": "Randomized phase 2 obesity trial", "population": "Adults with obesity", "parent_trial_n": "", "body_composition_n": "", "treatment_n": "", "comparator_n": "", "dose": "30 mg/kg", "duration_weeks": 72, "method": "Body-composition assessment", "body_region": "Whole body", "estimand": "Efficacy estimand", "body_weight_change": "-10.8%", "fat_change": "-28.5%", "lean_change": "+2.5%", "fat_share_pct": 100.0, "lean_share_pct": "", "metric_provenance": "Direct trial result", "functional_result": "Not used as an approved-product recommendation", "comparability_notes": "Investigational phase 2 result; demonstrates that the fat-versus-lean partition can be modified.", "publish_status": "Publish in investigational context", "source_url": "https://doi.org/10.1038/s41591-026-04204-0" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Investigational body-composition modification evidence", "active_ingredient_or_regimen": "Semaglutide", "product_context": "BELIEVE active comparator", "regulatory_status": "FDA-approved ingredient/dose context", "study": "BELIEVE week-72 analysis", "study_design": "Randomized phase 2 obesity trial", "population": "Adults with obesity", "parent_trial_n": "", "body_composition_n": "", "treatment_n": "", "comparator_n": "", "dose": "2.4 mg once weekly", "duration_weeks": 72, "method": "Body-composition assessment", "body_region": "Whole body", "estimand": "Efficacy estimand", "body_weight_change": "-15.7%", "fat_change": "-27.8%", "lean_change": "-7.4%", "fat_share_pct": 75.6, "lean_share_pct": "", "metric_provenance": "Direct trial result", "functional_result": "Not used as a head-to-head approved-product ranking", "comparability_notes": "Phase 2 active comparator within a trial of an investigational agent.", "publish_status": "Publish in investigational context", "source_url": "https://doi.org/10.1038/s41591-026-04204-0" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Investigational body-composition modification evidence", "active_ingredient_or_regimen": "Bimagrumab + semaglutide", "product_context": "BELIEVE high-dose combination", "regulatory_status": "Investigational combination", "study": "BELIEVE week-72 analysis", "study_design": "Randomized phase 2 obesity trial", "population": "Adults with obesity", "parent_trial_n": "", "body_composition_n": "", "treatment_n": "", "comparator_n": "", "dose": "High-dose bimagrumab + semaglutide 2.4 mg", "duration_weeks": 72, "method": "Body-composition assessment", "body_region": "Whole body", "estimand": "Efficacy estimand", "body_weight_change": "-22.1%", "fat_change": "-45.7%", "lean_change": "-2.9%", "fat_share_pct": 92.2, "lean_share_pct": "", "metric_provenance": "Direct trial result", "functional_result": "Not used as a current-treatment recommendation", "comparability_notes": "Investigational phase 2 combination; demonstrates modifiability of weight-loss composition.", "publish_status": "Publish in investigational context", "source_url": "https://doi.org/10.1038/s41591-026-04204-0" }, { "dataset_version": "1.0", "verified_date": "2026-08-01", "evidence_tier": "Observational comparative context", "active_ingredient_or_regimen": "Tirzepatide versus semaglutide", "product_context": "Routine-care comparison", "regulatory_status": "Both ingredients FDA-approved in relevant U.S. product contexts", "study": "Routine-care body-composition digital phenotyping preprint", "study_design": "Nonrandomized observational preprint using EHR-linked measurements", "population": "Routine-care first-episode semaglutide or tirzepatide users", "parent_trial_n": 670422, "body_composition_n": 7965, "treatment_n": "", "comparator_n": "", "dose": "Heterogeneous routine-care exposure", "duration_weeks": 52, "method": "Clinical body-composition measurements with EHR/LLM phenotyping", "body_region": "Heterogeneous routine-care measurements", "estimand": "Observational association", "body_weight_change": "", "fat_change": "", "lean_change": "Tirzepatide associated with 1.1 to 2.0 percentage points greater relative lean-body-mass decline across assessed timepoints", "fat_share_pct": "", "lean_share_pct": "", "metric_provenance": "Observational preprint", "functional_result": "Not established", "comparability_notes": "Nonrandomized treatment selection, heterogeneous measurement and preprint status prevent causal interpretation.", "publish_status": "Publish in separate observational context", "source_url": "https://www.medrxiv.org/content/10.64898/2026.04.11.26350687v1" } ], "negative_search_log": [ { "medicine_or_formulation": "Wegovy tablets — semaglutide 25 mg once daily", "outcome_sought": "Quantitative whole-body lean-mass share in an adult obesity population", "source_set_reviewed": [ "OASIS obesity trial publications", "FDA prescribing information", "PubMed and DOI-indexed primary literature" ], "result": "NQL — no qualifying whole-body lean-share result located under the published protocol", "verified_date": "2026-08-01" }, { "medicine_or_formulation": "Wegovy HD — semaglutide 7.2 mg once weekly", "outcome_sought": "Dose-specific whole-body lean-mass share for the 7.2 mg group", "source_set_reviewed": [ "STEP UP publications and congress materials", "FDA approval materials", "PubMed and DOI-indexed primary literature" ], "result": "NQL — the located STEP UP body-composition analysis pooled 2.4 mg and 7.2 mg and used regional MRI", "verified_date": "2026-08-01" }, { "medicine_or_formulation": "Zepbound — tirzepatide 5, 10 and 15 mg once weekly", "outcome_sought": "Dose-specific whole-body lean-mass share for each maintenance dose", "source_set_reviewed": [ "SURMOUNT-1 body-composition publication and correction", "FDA prescribing information", "PubMed and DOI-indexed primary literature" ], "result": "NQL — the qualifying SURMOUNT-1 body-composition result pooled the three doses", "verified_date": "2026-08-01" }, { "medicine_or_formulation": "Foundayo — marketed orforglipron strengths", "outcome_sought": "Whole-body lean-mass share reported separately by current marketed strength", "source_set_reviewed": [ "ATTAIN-1 primary publication", "FDA prescribing information", "PubMed and DOI-indexed primary literature" ], "result": "NQL — the qualifying body-composition analysis pooled publication-dose groups and did not report current marketed strengths separately", "verified_date": "2026-08-01" } ] }