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

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: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Retatrutide (LY3437943); Drug: Placebo; Behavioral: Standardized diet and physical activity counseling throughout the study.

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: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Seni S Lu, Phd; Phone Number: +86 13076790030; Email: Seni-Lu@beijing-biotech.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518036
      • Recruiting
      • Peking University Shenzhen Hospital
      • Contact: Zhen J Peng, Phd; Phone Number: +8613076790039; Email: Zhen-Peng@beijing-biotech.com

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Time Frame
Mean percent change in body weight from randomization/baseline to Week 24.	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean percent change in body weight from baseline to Week 48	48 weeks
Proportion of participants achieving ≥5%, ≥10%, and ≥15% body weight reduction at Weeks 24 and 48.	48 weeks
Mean change in body weight (kg) at Weeks 24 and 48.	48 weeks
Mean change in BMI (kg/m²) at Weeks 24 and 48.	48 weeks
Mean change in waist circumference (cm) at Weeks 24 and 48	48 weeks
Safety and tolerability outcomes (e.g., treatment-emergent adverse events; serious adverse events; discontinuations due to adverse events).	48 weeks

Collaborators and Investigators

• Sponsor: Hudson Biotech

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): February 17, 2028

Study Registration Dates

• First Submitted: March 8, 2026
• First Submitted That Met QC Criteria: March 8, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: weight loss; BMI; body weight; GLP-1 receptor agonist; waist circumference; lifestyle counseling; Retatrutide; LY3437943; triple agonist; GIP receptor agonist; glucagon receptor agonist
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight Changes; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Weight Loss; Body Weight; retatrutide
• Other Study ID 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