Retatrutide compared with placebo in adults with obesity or overweight

Trial details

Who runs it

Hudson Biotech

Trial code

NCT07467447

Record updated

12 March 2026

Original description

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.Read full original descriptionShow less

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.

Inclusion: 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: 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); Clinically significant gastric emptying abnormality (e.g., severe gastroparesis) or chronic drugs affecting GI motility; Organ transplant history (except corneal transplant) or awaiting transplant; 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); Started implantable/injectable contraceptives within 18 months prior to screening (IUDs allowed if used ≥3 months); Previously received LY3437943 in this or another study; History of diabetes mellitus (type 1 or type 2), ketoacidosis, or hyperosmolar state/coma; History of acute or chronic pancreatitis (exception for resolved gallstone pancreatitis post-cholecystectomy); 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; Elevated calcitonin at Visit 1 per protocol thresholds; personal/family history of medullary thyroid carcinoma or MEN2; Contraindication to GLP-1 receptor agonists, or other conditions that could prevent protocol compliance (including drug/alcohol abuse or eating disorder), per investigator judgment; Severe atopy/multiple severe allergies or severe hypersensitivity reactions; 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); Known allergies to GLP-1 receptor agonists or LY3437943; Screening lab values suggestive of diabetes (HbA1c ≥6.5%; fasting glucose ≥126 mg/dL; or random glucose ≥200 mg/dL); Renal impairment: eGFR <45 mL/min/1.73 m² (CKD-EPI) at screening; 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); Hematologic conditions interfering with HbA1c measurement; recent large blood donation/transfusion/severe blood loss; hemoglobin below protocol thresholds; Fasting triglycerides >500 mg/dL at screening (with stability requirement for lipid-lowering therapy); Use of metformin or other glucose-lowering medications (e.g., for PCOS or diabetes prevention) not permitted at entry; Active/untreated malignancy or remission <5 years (with protocol exceptions for certain in-situ/skin cancers); TSH outside 0.4 to 6.0 mIU/L at screening (with protocol-defined exceptions); 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); Currently enrolled in another investigational study or recent participation/treatment within 30 days (or 5 half-lives, whichever longer); 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).

ClinicalTrials.gov NCT07467447