EMBRAZE
Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial
Pratley RE et al. · Nature Medicine
Study record
- Population
102 adults randomized, 51 per group; ages 18–65 with overweight plus a weight-related condition or obesity. Most participants were women. The primary efficacy population comprised 43 apitegromab and 44 placebo completers; safety included all 51 treated participants per arm. Broad medical exclusions limit generalizability.
Read source · Full-text reportMethods — Participants and Statistical analysis; Table 1- Formulation
Tirzepatide injection pen plus intravenous apitegromab, an investigational monoclonal antibody, or intravenous placebo. Detailed antibody preparation is not fully verified; this is not evidence for a commercial peptide blend.
Inspect extraction gap · Full-text reportMethods — Procedures- Route
Weekly subcutaneous tirzepatide in both groups; intravenous apitegromab or placebo.
Read source · Full-text reportMethods — Procedures- Dose & frequency
Apitegromab 10 mg/kg every four weeks or placebo, both with tirzepatide starting at 2.5 mg weekly and increasing by 2.5 mg every four weeks as tolerated, up to 15 mg. Standard lifestyle counseling was provided. This supervised combination trial does not establish a personal stack.
Read source · Full-text reportMethods — Procedures; Table 2 arm labels- Study design
Phase 2 trial randomized 1:1; sponsor, participants and investigators masked, site pharmacist unmasked. Primary analysis used treatment completers with baseline and week-24 DEXA, with 80% confidence intervals and nominal P values without multiplicity adjustment. Supportive ITT analyses are separate.
Read source · Full-text reportMethods — Procedures and Statistical analysis- Duration
24 weeks of treatment followed by 16 weeks without study treatments for safety follow-up. The follow-up period is not a validated on/off dosing cycle.
Read source · Full-text reportMethods — Procedures- Reported findings
Week-24 adjusted lean-mass change was −1.6 kg with apitegromab versus −3.5 kg with placebo, both alongside tirzepatide: difference 1.9 kg (80% CI 1.2–2.7), nominal P=0.0014. No significant total-weight or absolute fat-mass difference was found, and exploratory physical-function assessments showed no notable difference.
Read source · Full-text reportTable 2; Results — efficacy; Methods — Statistical analysis- Adverse events
Through week 40, adverse events occurred in 39/51 versus 36/51; serious events in 1/51 each; events leading to study-drug discontinuation in 2/51 versus 3/51. Any-event risk difference was 6 percentage points (95% CI −11 to 22). These small groups do not establish safety equivalence.
Read source · Full-text reportResults — Safety; Table 3 and footnotes- Monitoring
Safety assessments included adverse events, laboratory tests, vital signs, ECGs and anti-drug antibodies. Three of 51 apitegromab recipients had transient low-titer antibodies; authors reported no associated notable safety events. Assessment detail in image-only extended-data tables remains incompletely extracted.
Read source · Full-text reportResults — Safety; Table 3; Extended Data Table 4 reference
What it supports
Provides phase 2 evidence of less DEXA-measured lean-mass loss when apitegromab was added to tirzepatide in a selected adult population.
What it does not establish
DEXA lean mass includes nonmuscle tissue and depends on hydration; less lean-mass loss does not prove greater strength. The reported 54.9% is relative reduction in lean-mass loss, not preservation of 54.9% of starting muscle. Primary results are from 87 completers, not all 102 randomized participants. Small selected cohort, short efficacy follow-up, 80% efficacy intervals and exploratory testing limit inference. No semaglutide-treated participants were enrolled despite broader protocol provisions. Extended-data numerical review remains pending. Extended-data sex analyses were post hoc with only seven and eight men; they do not establish a sex-based treatment rule. Physical-function tables use endpoint-specific completer counts, and routine lifestyle adherence was not monitored.
Funding
Scholar Rock funded the study and participated in design, conduct, data collection/management/analysis and manuscript review; multiple authors were sponsor employees.
Literature search cutoff: 2026-09-08 · Not independently clinically reviewed
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