Effect of LY3437943 Versus Placebo in Participants Who Have Obesity or Are Overweight (GZBF)

March 8, 2026 updated by: Hudson Biotech

A Phase 2 Study of Once-Weekly LY3437943 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities

Phase 2, multicenter, randomized, double-blind, placebo-controlled study evaluating once-weekly subcutaneous retatrutide (LY3437943) at multiple maintenance dose levels versus placebo in adults with obesity or overweight with weight-related comorbidities (without type 2 diabetes), alongside standardized diet and physical activity counseling.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

After screening (up to 6 weeks), eligible participants are randomized to one of several dose-escalation regimens leading to maintenance doses of 1, 4, 8, or 12 mg retatrutide (or placebo) administered once weekly for 48 weeks, followed by a 4-week safety follow-up. Two maintenance dose levels (4 mg and 8 mg) include alternative escalation schedules to evaluate tolerability. The primary efficacy evaluation is at Week 24 (percent change in body weight), with additional weight, anthropometric, and safety assessments through Week 48.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 to 75 years (inclusive) at time of informed consent.
  • BMI ≥30 and ≤50 kg/m², OR BMI ≥27 and <30 kg/m² with at least 1 weight-related comorbidity (hypertension; dyslipidemia; or cardiovascular disease such as ischemic CVD or NYHA Class I-II heart failure).
  • Motivated and able/willing to self-inject (or have trained assistance if needed) and follow study procedures, including lifestyle advice and questionnaires.
  • Subgroup (NAFLD addendum): liver fat content ≥10% by MRI-PDFF (for participants invited to the addendum).
  • Male and/or female; contraception requirements apply; women of childbearing potential must have negative pregnancy tests at specified visits and should not be breastfeeding.
  • Capable of giving signed informed consent and complying with protocol requirements.

Exclusion Criteria:

  • History of diabetes mellitus (type 1 or type 2), ketoacidosis, or hyperosmolar state/coma.
  • Screening lab values suggestive of diabetes (HbA1c ≥6.5%; fasting glucose ≥126 mg/dL; or random glucose ≥200 mg/dL).
  • Self-reported change in body weight >5 kg within 3 months prior to screening.
  • Prior or planned surgical treatment for obesity (exceptions: liposuction/abdominoplasty >1 year prior).
  • Current/planned endoscopic or device-based obesity therapy, or device removal within last 6 months (e.g., intragastric balloon, gastric artery embolization).
  • Renal impairment: eGFR <45 mL/min/1.73 m² (CKD-EPI) at screening.
  • Clinically significant gastric emptying abnormality (e.g., severe gastroparesis) or chronic drugs affecting GI motility.
  • History of acute or chronic pancreatitis (exception for resolved gallstone pancreatitis post-cholecystectomy).
  • TSH outside 0.4 to 6.0 mIU/L at screening (with protocol-defined exceptions).
  • Obesity due to other endocrine disorders (e.g., Cushing's) or monogenic/syndromic obesity (e.g., Prader-Willi).
  • Psychiatric exclusion criteria including unstable major depressive disorder/severe psychiatric disorder within 2 years; lifetime suicide attempt; PHQ-9 score ≥15; or specified Columbia-Suicide Severity Rating Scale (C-SSRS) findings within past month.
  • Uncontrolled hypertension (systolic ≥160 mmHg and/or diastolic ≥100 mmHg) or elevated resting pulse rate (>100 bpm) at baseline.
  • Recent (within 3 months) major cardiovascular events (e.g., MI, stroke, unstable angina, CHF hospitalization); tachyarrhythmia syndromes; NYHA Class III-IV CHF; or ECG abnormalities interfering with interpretation.
  • Acute/chronic hepatitis or liver disease other than NAFLD; or screening labs: ALT >3× ULN, ALP >1.5× ULN, or total bilirubin >1.5× ULN (with exception).
  • Elevated calcitonin at Visit 1 per protocol thresholds; personal/family history of medullary thyroid carcinoma or MEN2.
  • Active/untreated malignancy or remission <5 years (with protocol exceptions for certain in-situ/skin cancers).
  • Contraindication to GLP-1 receptor agonists, or other conditions that could prevent protocol compliance (including drug/alcohol abuse or eating disorder), per investigator judgment.
  • Alcohol consumption >14 units/week (women) or >21 units/week (men).
  • Recent marijuana/THC-containing product use within 3 months or unwillingness to abstain during trial (protocol exception for cannabidiol oil if agrees to refrain).
  • Organ transplant history (except corneal transplant) or awaiting transplant.
  • Hematologic conditions interfering with HbA1c measurement; recent large blood donation/transfusion/severe blood loss; hemoglobin below protocol thresholds.
  • Severe atopy/multiple severe allergies or severe hypersensitivity reactions.
  • Fasting triglycerides >500 mg/dL at screening (with stability requirement for lipid-lowering therapy).
  • Significant active, uncontrolled medical condition or history posing risk or interfering with data interpretation, per investigator judgment.
  • History of symptomatic gallbladder disease within past 2 years (protocol-defined exceptions after cholecystectomy).
  • History of documented HIV infection.
  • Chronic systemic glucocorticoid therapy within 3 months or active autoimmune abnormality likely to require systemic steroids during study (with specified formulation exceptions).
  • Recent medications that may cause significant weight gain (e.g., tricyclic antidepressants, atypical antipsychotics, mood stabilizers) within 3 months.
  • Recent use (within 3 months) of medications or remedies intended to promote weight loss (examples listed in protocol, including GLP-1 RAs).
  • Use of metformin or other glucose-lowering medications (e.g., for PCOS or diabetes prevention) not permitted at entry.
  • Started implantable/injectable contraceptives within 18 months prior to screening (IUDs allowed if used ≥3 months).
  • Known allergies to GLP-1 receptor agonists or LY3437943.
  • Currently enrolled in another investigational study or recent participation/treatment within 30 days (or 5 half-lives, whichever longer).
  • Previously received LY3437943 in this or another study.
  • Investigator site personnel directly affiliated with the study and/or their immediate family; or Lilly employees.
  • Note: The publicly posted protocol references additional exclusion criteria numbered 52-57 in a separate protocol addendum (not included in the posted protocol PDF).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Retatrutide (LY3437943) 1 mg once weekly (no escalation)
Drug: Retatrutide (LY3437943)
subcutaneous injection, once weekly (dose per assigned arm).
Drug: Placebo
subcutaneous injection, once weekly (schedule matched to an active arm).
Behavioral: Standardized diet and physical activity counseling throughout the study.
Standardized diet and physical activity counseling throughout the study.
Experimental: Retatrutide 4 mg once weekly, escalation subgroup (a): 2 mg → 4 mg.
Drug: Retatrutide (LY3437943)
subcutaneous injection, once weekly (dose per assigned arm).
Drug: Placebo
subcutaneous injection, once weekly (schedule matched to an active arm).
Behavioral: Standardized diet and physical activity counseling throughout the study.
Standardized diet and physical activity counseling throughout the study.
Experimental: Retatrutide 4 mg once weekly, subgroup (b): start 4 mg (no escalation).
Drug: Retatrutide (LY3437943)
subcutaneous injection, once weekly (dose per assigned arm).
Drug: Placebo
subcutaneous injection, once weekly (schedule matched to an active arm).
Behavioral: Standardized diet and physical activity counseling throughout the study.
Standardized diet and physical activity counseling throughout the study.
Experimental: Retatrutide 8 mg once weekly, subgroup (a): 2 mg → 4 mg → 8 mg
Drug: Retatrutide (LY3437943)
subcutaneous injection, once weekly (dose per assigned arm).
Drug: Placebo
subcutaneous injection, once weekly (schedule matched to an active arm).
Behavioral: Standardized diet and physical activity counseling throughout the study.
Standardized diet and physical activity counseling throughout the study.
Experimental: Retatrutide 12 mg once weekly: 2 mg → 4 mg → 8 mg → 12 mg.
Drug: Retatrutide (LY3437943)
subcutaneous injection, once weekly (dose per assigned arm).
Drug: Placebo
subcutaneous injection, once weekly (schedule matched to an active arm).
Behavioral: Standardized diet and physical activity counseling throughout the study.
Standardized diet and physical activity counseling throughout the study.
Experimental: Placebo once weekly (matched escalation schedule to maintain blinding).
Drug: Retatrutide (LY3437943)
subcutaneous injection, once weekly (dose per assigned arm).
Drug: Placebo
subcutaneous injection, once weekly (schedule matched to an active arm).
Behavioral: Standardized diet and physical activity counseling throughout the study.
Standardized diet and physical activity counseling throughout the study.
Experimental: Retatrutide 8 mg once weekly, subgroup (b): 4 mg → 8 mg.
Drug: Retatrutide (LY3437943)
subcutaneous injection, once weekly (dose per assigned arm).
Drug: Placebo
subcutaneous injection, once weekly (schedule matched to an active arm).
Behavioral: Standardized diet and physical activity counseling throughout the study.
Standardized diet and physical activity counseling throughout the study.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Mean percent change in body weight from randomization/baseline to Week 24.
Time Frame: 24 weeks
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Mean percent change in body weight from baseline to Week 48
Time Frame: 48 weeks
48 weeks
Proportion of participants achieving ≥5%, ≥10%, and ≥15% body weight reduction at Weeks 24 and 48.
Time Frame: 48 weeks
48 weeks
Mean change in body weight (kg) at Weeks 24 and 48.
Time Frame: 48 weeks
48 weeks
Mean change in BMI (kg/m²) at Weeks 24 and 48.
Time Frame: 48 weeks
48 weeks
Mean change in waist circumference (cm) at Weeks 24 and 48
Time Frame: 48 weeks
48 weeks
Safety and tolerability outcomes (e.g., treatment-emergent adverse events; serious adverse events; discontinuations due to adverse events).
Time Frame: 48 weeks
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hudson Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 15, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 14, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 17, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 12, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • J1I-MC-GZBF (Eli Lilly and Company)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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