Primary outcomeLeast squares mean· Baseline, Week 32
Percent Change From Baseline in Body Weight at Week 32
| Group | Value (percent change) | Spread |
|---|---|---|
| Placebo | -0.85 | 0.787 |
| 3/6 mg Mazdutide | -7.33 | 0.937 |
| 10 mg Mazdutide | -15.6 | 0.744 |
| 16 mg Mazdutide | -18.1 | 0.965 |
Trial · Interventional
CompletedPhase 2Results postedRegistry dataA Study of LY3305677 Compared With Placebo in Adult Participants With Obesity or Overweight
NCTNCT06124807 (opens ClinicalTrials.gov in a new tab)Other id18661Other idW8M-MC-OXA1Other idCWMM Master Protocol
Overview
- Status
- Completed
- Phase
- Phase 2
- Enrollment
- 179 participants (actual)
- Sponsor
- Eli Lilly and Company · Industry
- Design
- Randomized · Double masking
- Countries
1 country
United States
- Start
- 17 Nov 2023
- Primary completion
- 22 Jan 2025
- Completion
- 9 Jul 2025
- First posted
- 9 Nov 2023
- Last update posted
- 21 Apr 2026
- Conditions
- Obesity · Overweight and Obesity
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
2023202420252026
- Ph 2
A Study of LY3305677 Compared With Placebo in Adult Participants With Obesity or Overweight
NCT0612480717 Nov 2023 to 9 Jul 2025
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Interventions
- MazdutideDrug
- PlaceboDrug
Arms4
Experimental
3/6 Milligrams (mg) Mazdutide
Participants received once-weekly subcutaneous Mazdutide with dose escalation until the target dose (3 or 6 mg) was achieved, starting at 1.5 mg from Weeks 0-3, followed by 3 mg from Weeks 4-31, then 6 mg from Weeks 32-48.
Experimental
10 mg Mazdutide
Participants received once-weekly subcutaneous Mazdutide with dose escalation until the target dose (10 mg) was achieved, starting at 1.5 mg from Weeks 0-3, followed by 3 mg from Weeks 4-7, 6 mg from Weeks 8-11, 8 mg from Weeks 12-15, and then 10 mg from Weeks 16-48.
Experimental
16 mg Mazdutide
Participants received once-weekly subcutaneous Mazdutide with dose escalation until the target dose (16 mg) was achieved, starting at 1.5 mg from Weeks 0-3, followed by 3 mg from Weeks 4-7, 6 mg from Weeks 8-11, 9 mg from Weeks 12-15, 12 mg from Weeks 16-19, and then16 mg from Weeks 20-48.
Placebo comparator
Placebo
Participants received Mazdutide matched placebo subcutaneously once weekly from Weeks 0 to 48.
Primary outcomes1
Outcomes the sponsor listed as primary.
Percent Change From Baseline in Body Weight at Week 32
Time frame · Baseline, Week 32
Registry description
Least squares means were calculated using an MMRM model for post-baseline measures: Variable = Baseline\*Time + Strata\*Time + Treatment\*Time, where Treatment and Strata are factors. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (\<=30, \>30 kg/m\^2).
Secondary outcomes(14)
Percent Change From Baseline in Body Weight at Week 48
Time frame · Baseline, Week 48
Registry description
Least squares means were calculated using an MMRM model for post-baseline measures: Variable = Baseline\*Time + Strata\*Time + Treatment\*Time, where Treatment and Strata are factors. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (\<=30, \>30 kg/m\^2).
Change From Baseline in Body Weight
Time frame · Baseline, Week 32, Week 48
Registry description
Least squares means were calculated using an MMRM model for post-baseline measures: Variable = Baseline\*Time + Strata\*Time + Treatment\*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (\<=30, \>30 kg/m\^2).
Mean Percentage of Participants Who Achieve ≥5% Body Weight Reduction
Time frame · Baseline, Week 32, Week 48
Registry description
Mean percentage of participants who achieve ≥5% body weight reduction was calculated using imputed data with the logistic regression model Variable = Baseline + Treatment + Strata (Sex), where Treatment and Strata (Sex) are factors. Mean percentage of participants was calculated by combining percentage of participants achieving target at week 32 and week 48 respectively in imputed data sets using Rubin's rule.
Mean Percentage of Participants Who Achieve ≥10% Body Weight Reduction
Time frame · Baseline, Week 32, Week 48
Registry description
Mean percentage of participants who achieve ≥10% body weight reduction was calculated using imputed data with the logistic regression model Variable = Baseline + Treatment + Strata (Sex), where Treatment and Strata (Sex) are factors. Mean percentage of participants was calculated by combining percentage of participants achieving target at week 32 and week 48 respectively in imputed data sets using Rubin's rule.
Change From Baseline in Body Mass Index (BMI)
Time frame · Baseline, Week 32, Week 48
Registry description
Least squares means were calculated using an MMRM model for post-baseline measures: Variable = Baseline\*Time + Strata\*Time + Treatment\*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (\<=30, \>30 kg/m\^2).
Number of Participants With Treatment Emergent Anti-drug Antibodies (TE-ADAs)
Time frame · Baseline up to week 56
Registry description
Blood samples were tested to determine if a participant reacted to Mazdutide by producing anti-Mazdutide antibodies. A participant is TE ADA evaluable if there is at least one non-missing test result for ADA for each of the baseline period and the postbaseline period. A TE ADA evaluable participant is considered to be TE ADA+ if the participant has at least one postbaseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the subject is TE ADA+ if there is at least one postbaseline result of ADA Present with titer \>=1:20.
Pharmacokinetics (PK): Area Under the Curve (AUC) of Mazdutide at Steady State
Time frame · Predose at Week 0, Week 4, Week 8, Week 12, Week 24, Week 32, Week 48; Post dose (2 to 6 hours after dosing) at Week 0, Week 12, Week 24
Registry description
PK samples were analyzed using a population PK approach to estimate AUC at steady state. Data presented are Geometric mean with 90% prediction interval.
PK: Maximum Concentration (Cmax) of Mazdutide at Steady State
Time frame · Predose at Week 0, Week 4, Week 8, Week 12, Week 24, Week 32, Week 48; Post dose (2 to 6 hours after dosing) at Week 0, Week 12, Week 24
Registry description
PK samples were analyzed using a population PK approach to estimate Cmax at steady state. Data presented are Geometric mean with 90% prediction interval.
Change From Baseline in Liver Fat Content (LFC) by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in Participants With Baseline LFC >=5%
Time frame · Baseline, Week 32, Week 48
Registry description
Least squares means were calculated using an MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = Treatment\*Time + log(Baseline)\*Time + Strata\*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (\<=30, \>30 kg/m\^2).
Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=5%
Time frame · Baseline, Week 32, Week 48
Registry description
Least squares means were calculated using an MMRM model for post-baseline measures: log (Actual Measurement/Baseline) = Treatment\*Time + log (Baseline)\*Time + Strata\*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (\<=30, \>30 kg/m\^2).
Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%
Time frame · Baseline, Week 32, Week 48
Registry description
Least squares means were calculated using an MMRM model for post-baseline measures: log (Actual Measurement/Baseline) = Treatment\*Time + log (Baseline)\*Time + Strata\*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (\<=30, \>30 kg/m\^2).
Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%
Time frame · Baseline, Week 32, Week 48
Registry description
Least squares means were calculated using an MMRM model for post-baseline measures: log (Actual Measurement/Baseline) = Treatment\*Time + log (Baseline)\*Time + Strata\*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (\<=30, \>30 kg/m\^2).
Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >= 5% Who Achieved >30% Relative Reduction in LFC
Time frame · Baseline, Week 32, Week 48
Registry description
mean Percentage of participants with baseline liver fat content (LFC) \>= 5% who achieved \>30% relative reduction in LFC was estimated using imputed data with the logistic regression model Variable = Baseline + Treatment + Strata (Sex), where Treatment and Strata (Sex) are factors. Mean percentage of participants was calculated by combining percentage of participants achieving target at week 32 and week 48 respectively in imputed data sets using Rubin's rule.
Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >=10% Who Achieved >30% Relative Reduction in LFC
Time frame · Baseline, Week 32, Week 48
Registry description
Mean Percentage of participants with baseline liver fat content (LFC) \>=10% who achieved \>30% relative reduction in LFC was estimated using imputed data with the logistic regression model Variable = Baseline + Treatment + Strata (Sex), where Treatment and Strata (Sex) are factors. Mean percentage of participants was calculated by combining percentage of participants achieving target at week 32 and week 48 respectively in imputed data sets using Rubin's rule.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(7)
Secondary outcomeLeast squares mean· Baseline, Week 48
Percent Change From Baseline in Body Weight at Week 48
| Group | Value (percent change) | Spread |
|---|---|---|
| Placebo | -0.047 | 1.059 |
| 3/6 mg Mazdutide | -10.54 | 1.498 |
| 10 mg Mazdutide | -19.2 | 1.076 |
| 16 mg Mazdutide | -22.3 | 1.424 |
Secondary outcomeLeast squares mean· Baseline, Week 32, Week 48
Change From Baseline in Body Weight
| Group | Value (Kilograms (Kg)) | Spread |
|---|---|---|
| Placebo | -0.98 | 0.882 |
| 3/6 mg Mazdutide | -7.79 | 1.011 |
| 10 mg Mazdutide | -16.1 | 0.779 |
| 16 mg Mazdutide | -19.2 | 1.037 |
Secondary outcomeMean· Baseline, Week 32, Week 48
Mean Percentage of Participants Who Achieve ≥5% Body Weight Reduction
| Group | Value (percentage of participants) | Spread |
|---|---|---|
| Placebo | 23.97 | 6.99 |
| 3/6 mg Mazdutide | 67.64 | 8.70 |
| 10 mg Mazdutide | 96.10 | 3.57 |
| 16 mg Mazdutide | 92.23 | 4.30 |
Secondary outcomeMean· Baseline, Week 32, Week 48
Mean Percentage of Participants Who Achieve ≥10% Body Weight Reduction
| Group | Value (percentage of participants) | Spread |
|---|---|---|
| Placebo | 8.73 | 4.53 |
| 3/6 mg Mazdutide | 45.43 | 9.18 |
| 10 mg Mazdutide | 85.95 | 5.67 |
| 16 mg Mazdutide | 77.08 | 6.45 |
Secondary outcomeLeast squares mean· Baseline, Week 32, Week 48
Change From Baseline in Body Mass Index (BMI)
| Group | Value (kilogram per square metre (kg/m^2)) | Spread |
|---|---|---|
| Placebo | -0.32 | 0.305 |
| 3/6 mg Mazdutide | -2.84 | 0.376 |
| 10 mg Mazdutide | -5.81 | 0.281 |
| 16 mg Mazdutide | -6.86 | 0.372 |
Secondary outcomeCount of participants· Baseline up to week 56
Number of Participants With Treatment Emergent Anti-drug Antibodies (TE-ADAs)
| Group | Value (Participants) |
|---|---|
| Placebo | 5 |
| 3/6 Milligrams (mg) Mazdutide | 3 |
| 10 mg Mazdutide | 10 |
| 16 mg Mazdutide | 11 |
Secondary outcomeGeometric mean· Predose at Week 0, Week 4, Week 8, Week 12, Week 24, Week 32, Week 48; Post dose (2 to 6 hours after dosing) at Week 0, Week 12, Week 24
Pharmacokinetics (PK): Area Under the Curve (AUC) of Mazdutide at Steady State
| Group | Value (nanogram*hour per milliliter (ng*h/mL)) |
|---|---|
| 3 mg Mazdutide | 93800 |
| 6 mg Mazdutide | 190000 |
| 10 mg Mazdutide | 340000 |
| 16 mg Mazdutide | 537000 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| PlaceboParticipants received Mazdutide matched placebo subcutaneously once weekly from Weeks 0 to 48 | 0 / 47 | 1 / 47 | 34 / 47 |
| 3/6 Milligrams (mg) MazdutideParticipants received once-weekly subcutaneous Mazdutide with dose escalation until the target dose (3 or 6 mg) was achieved, starting at 1.5 mg from Weeks 0-3, followed by 3 mg from Weeks 4-31, then 6 mg from Weeks 32-48. | 0 / 32 | 1 / 32 | 29 / 32 |
| 10 mg MazdutideParticipants received once-weekly subcutaneous Mazdutide with dose escalation until the target dose (10 mg) was achieved, starting at 1.5 mg from Weeks 0-3, followed by 3 mg from Weeks 4-7, 6 mg from Weeks 8-11, 8 mg from Weeks 12-15, and then 10 mg from Weeks 16-48. | 0 / 47 | 1 / 47 | 37 / 47 |
| 16 mg MazdutideParticipants received once-weekly subcutaneous Mazdutide with dose escalation until the target dose (16 mg) was achieved, starting at 1.5 mg from Weeks 0-3, followed by 3 mg from Weeks 4-7, 6 mg from Weeks 8-11, 9 mg from Weeks 12-15, 12 mg from Weeks 16-19, and then 16 mg from Weeks 20-48. | 0 / 51 | 2 / 51 | 45 / 51 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies1
Studies that cite this trial.
Studies with results
1 study on this page
PubMed tag: none · 2026
7 results
Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial.
Hsia et al. 2026The lancet. Diabetes & endocrinology
PMID 42628555DOI 10.1016/s2213-8587(26)00160-9PUB-42628555
Full text at the publisher7 results
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years up to 75 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
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.
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