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

NCT07467447 | Recruiting Phase 2 DMC

• 1 other identifier: J1I-MC-GZBF
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity

Keywords

Retatrutide; LY3437943; triple agonist; GIP receptor agonist; GLP-1 receptor agonist; glucagon receptor agonist; weight loss; body weight; BMI; waist circumference; lifestyle counseling

Outcome Measures

Primary Outcomes (1)

• Mean percent change in body weight from randomization/baseline to Week 24.

  24 weeks

Secondary Outcomes (6)

• 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

Study Arms (7)

Retatrutide (LY3437943) 1 mg once weekly (no escalation)

EXPERIMENTAL

Drug: Retatrutide (LY3437943); Drug: Placebo; Behavioral: Standardized diet and physical activity counseling throughout the study.

Retatrutide 4 mg once weekly, escalation subgroup (a): 2 mg → 4 mg.

EXPERIMENTAL

Drug: Retatrutide (LY3437943); Drug: Placebo; Behavioral: Standardized diet and physical activity counseling throughout the study.

Retatrutide 4 mg once weekly, subgroup (b): start 4 mg (no escalation).

EXPERIMENTAL

Drug: Retatrutide (LY3437943); Drug: Placebo; Behavioral: Standardized diet and physical activity counseling throughout the study.

Retatrutide 8 mg once weekly, subgroup (a): 2 mg → 4 mg → 8 mg

EXPERIMENTAL

Drug: Retatrutide (LY3437943); Drug: Placebo; Behavioral: Standardized diet and physical activity counseling throughout the study.

Retatrutide 12 mg once weekly: 2 mg → 4 mg → 8 mg → 12 mg.

EXPERIMENTAL

Drug: Retatrutide (LY3437943); Drug: Placebo; Behavioral: Standardized diet and physical activity counseling throughout the study.

Placebo once weekly (matched escalation schedule to maintain blinding).

EXPERIMENTAL

Drug: Retatrutide (LY3437943); Drug: Placebo; Behavioral: Standardized diet and physical activity counseling throughout the study.

Retatrutide 8 mg once weekly, subgroup (b): 4 mg → 8 mg.

EXPERIMENTAL

Drug: Retatrutide (LY3437943); Drug: Placebo; Behavioral: Standardized diet and physical activity counseling throughout the study.

Interventions

Retatrutide (LY3437943) DRUG

subcutaneous injection, once weekly (dose per assigned arm).

Placebo once weekly (matched escalation schedule to maintain blinding).; Retatrutide (LY3437943) 1 mg once weekly (no escalation); Retatrutide 12 mg once weekly: 2 mg → 4 mg → 8 mg → 12 mg.; Retatrutide 4 mg once weekly, escalation subgroup (a): 2 mg → 4 mg.; Retatrutide 4 mg once weekly, subgroup (b): start 4 mg (no escalation).; Retatrutide 8 mg once weekly, subgroup (a): 2 mg → 4 mg → 8 mg; Retatrutide 8 mg once weekly, subgroup (b): 4 mg → 8 mg.

Placebo DRUG

subcutaneous injection, once weekly (schedule matched to an active arm).

Placebo once weekly (matched escalation schedule to maintain blinding).; Retatrutide (LY3437943) 1 mg once weekly (no escalation); Retatrutide 12 mg once weekly: 2 mg → 4 mg → 8 mg → 12 mg.; Retatrutide 4 mg once weekly, escalation subgroup (a): 2 mg → 4 mg.; Retatrutide 4 mg once weekly, subgroup (b): start 4 mg (no escalation).; Retatrutide 8 mg once weekly, subgroup (a): 2 mg → 4 mg → 8 mg; Retatrutide 8 mg once weekly, subgroup (b): 4 mg → 8 mg.

Standardized diet and physical activity counseling throughout the study. BEHAVIORAL

Standardized diet and physical activity counseling throughout the study.

Placebo once weekly (matched escalation schedule to maintain blinding).; Retatrutide (LY3437943) 1 mg once weekly (no escalation); Retatrutide 12 mg once weekly: 2 mg → 4 mg → 8 mg → 12 mg.; Retatrutide 4 mg once weekly, escalation subgroup (a): 2 mg → 4 mg.; Retatrutide 4 mg once weekly, subgroup (b): start 4 mg (no escalation).; Retatrutide 8 mg once weekly, subgroup (a): 2 mg → 4 mg → 8 mg; Retatrutide 8 mg once weekly, subgroup (b): 4 mg → 8 mg.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• Hudson Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Obesity; Weight Loss; Body Weight

Interventions

retatrutide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: To preserve blinding, placebo participants follow an injection dose-escalation schedule matched to one of the active retatrutide arms.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants randomized to once-weekly subcutaneous retatrutide dose regimens (with dose escalation for selected arms) or placebo for 48 weeks, with standardized lifestyle counseling throughout.

Study Record Dates

• First Submitted: March 8, 2026
• First Posted: March 12, 2026
• Study Start: February 15, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): February 17, 2028
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

CN (1)