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Phase 2 N=179 Randomized Double-blind Treatment

A Study of LY3305677 Compared With Placebo in Adult Participants With Obesity or Overweight

Obesity · Overweight and Obesity

Enrolled (actual)
179
Serious AEs
2.8%
Results posted
Apr 2026
Primary outcome: Primary: Percent Change From Baseline in Body Weight at Week 32 — -0.85; -7.33; -15.6; -18.1 percent change

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Mazdutide (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Eli Lilly and Company
Primary completion
Jan 2025

Outcome Measures

OutcomeResultp-value
PRIMARY
Percent Change From Baseline in Body Weight at Week 32
-0.85; -7.33; -15.6; -18.1
SECONDARY
Percent Change From Baseline in Body Weight at Week 48
-0.047; -10.54; -19.2; -22.3
SECONDARY
Change From Baseline in Body Weight
-0.98; -7.79; -16.1; -19.2; -0.15; -11.15
SECONDARY
Mean Percentage of Participants Who Achieve ≥5% Body Weight Reduction
23.97; 67.64; 96.10; 92.23; 25.96; 74.77
SECONDARY
Mean Percentage of Participants Who Achieve ≥10% Body Weight Reduction
8.73; 45.43; 85.95; 77.08; 13.77; 57.86
SECONDARY
Change From Baseline in Body Mass Index (BMI)
-0.32; -2.84; -5.81; -6.86; -0.017; -4.07
SECONDARY
Number of Participants With Treatment Emergent Anti-drug Antibodies (TE-ADAs)
5; 3; 10; 11
SECONDARY
Pharmacokinetics (PK): Area Under the Curve (AUC) of Mazdutide at Steady State
93800; 190000; 340000; 537000
SECONDARY
PK: Maximum Concentration (Cmax) of Mazdutide at Steady State
694; 1420; 2530; 4020
SECONDARY
Change From Baseline in Liver Fat Content (LFC) by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in Participants With Baseline LFC >=5%
-1.62; -6.15; -7.78; -7.91; -1.35; -7.81
SECONDARY
Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=5%
-14.1; -53.5; -67.7; -68.8; -11.7; -68.0
SECONDARY
Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%
-4.3; -9.3; -13.8; -12.8; -4.6; -12.4
SECONDARY
Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%
-24.7; -53.4; -79.5; -73.6; -26.3; -71.2
SECONDARY
Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >= 5% Who Achieved >30% Relative Reduction in LFC
24.93; 73.97; 84.93; 83.40; 30.04; 87.73
SECONDARY
Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >=10% Who Achieved >30% Relative Reduction in LFC
38.57; 71.95; 99.71; 92.04; 36.82; 86.64

Summary

The main purpose of this study, performed under a master protocol W8M-MC-CWMM (NCT06143956), is to investigate weight management efficacy and safety with Mazdutide compared with placebo and in adult participants with obesity or overweight. The study will last about 62 weeks.

Eligibility Criteria

Inclusion Criteria

W8M-MC-OXA1:

  • Are males and females who agree to abide by the reproductive and contraceptive requirements

W8M-MC-CWMM:

  • Have a BMI ≥27 kilograms per square meter (kg/m²)

Exclusion Criteria

W8M-MC-OXA1:

  • Have any prior diagnosis of diabetes mellitus, that is type 2 diabetes mellitus (T2DM), or rare forms of diabetes mellitus, except gestational diabetes.
  • Have any of the following cardiovascular conditions within 6 months prior to screening:
  • acute myocardial infarction
  • cerebrovascular accident (stroke)
  • unstable angina, or
  • hospitalization due to congestive heart failure (CHF).
  • Have a history of New York Heart Association (NYHA) Functional Classification I-IV CHF.
  • Participants with hypertension who do not have well-controlled blood pressure (BP) (>140/90 mmHg), regardless of antihypertensive treatment. Participants receiving treatment for hypertension should be on a stable antihypertensive regimen for at least 3 months prior to screening.
  • Have a history of acute or chronic pancreatitis.

Note: If the investigator anticipates a need to add antihypertensive medication during the study, the participant should not be included in the ambulatory blood pressure monitoring (ABPM) procedures.

CWMM:

  • Have a prior or planned surgical treatment for obesity, except prior liposuction or abdominoplasty, if performed >1 year prior to screening.
  • Have type 1 diabetes mellitus, latent autoimmune diabetes in adults, or history of ketoacidosis or hyperosmolar coma.
  • Have poorly controlled hypertension.
  • Have signs and symptoms of any liver disease other than nonalcoholic fatty liver disease.
  • Have a history of symptomatic gallbladder disease within the past 2 years.
  • Have a lifetime history of suicide attempts.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT06124807). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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