Obesity
Conditions
Keywords
Retatrutide, LY3437943, triple agonist, GIP receptor agonist, GLP-1 receptor agonist, glucagon receptor agonist, weight loss, body weight, BMI, waist circumference, lifestyle counseling
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.
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.
Interventions
DRUGRetatrutide (LY3437943)
subcutaneous injection, once weekly (dose per assigned arm).
DRUGPlacebo
subcutaneous injection, once weekly (schedule matched to an active arm).
BEHAVIORALStandardized diet and physical activity counseling throughout the study.
Standardized diet and physical activity counseling throughout the study.
Sponsors
Hudson Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
To preserve blinding, placebo participants follow an injection dose-escalation schedule matched to one of the active retatrutide arms.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean percent change in body weight from randomization/baseline to Week 24. | 24 weeks |
Secondary
| 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 |
Countries
China
Contacts
CONTACTSeni S Lu, Phd
Outcome results
None listed