Effect of LY3437943 Versus Placebo in Participants Who Have Obesity or Are Overweight
NCT07467447
Phase
Phase 2
Recruitment status
Recruiting
Participants
Lead sponsor
Hudson Biotech
Start date
2026-02-15
Number of sites
- Summary
- 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.
- Acronym
- Short title
- Effect of LY3437943 Versus Placebo in Participants Who Have Obesity or Are Overweight
- Official title
- A Phase 2 Study of Once-Weekly LY3437943 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Recruiting
- Phase
- Phase 2
- Study type
- Interventional
- Completion date
- 2028-02-17
- First posted
- 2026-03-12
- Registry last updated
- 2026-03-12
- Primary completion date
- 2027-03-14
- Start date
- 2026-02-15
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Hudson Biotech
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT07467447
- ClinicalTrials.gov ID
- NCT07467447
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Parallel groups
- Purpose
- Treatment
- Masking
- Single masking
- Masking description
- To preserve blinding, placebo participants follow an injection dose-escalation schedule matched to one of the active retatrutide arms.
- Masked roles
- Participants
Sources for study design
Mean percent change in body weight from randomization/baseline to Week 24.
Timeframe: 24 weeks
Mean percent change in body weight from baseline to Week 48
Timeframe: 48 weeks
Proportion of participants achieving ≥5%, ≥10%, and ≥15% body weight reduction at Weeks 24 and 48.
Timeframe: 48 weeks
Mean change in body weight (kg) at Weeks 24 and 48.
Timeframe: 48 weeks
Mean change in BMI (kg/m²) at Weeks 24 and 48.
Timeframe: 48 weeks
Mean change in waist circumference (cm) at Weeks 24 and 48
Timeframe: 48 weeks
Safety and tolerability outcomes (e.g., treatment-emergent adverse events; serious adverse events; discontinuations due to adverse events).
Timeframe: 48 weeks
Sources for outcomes
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Maximum age
- 75 Years
- Healthy volunteers
- No
- 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.
- 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).
Sources for eligibility
- Peking University Shenzhen HospitalShenzhen, ChinaRecruiting
Sources for sites
Related records
Drugs (1)
Lead sponsors (1)
Conditions (1)
- Obesity disorder Primary condition