Obesity, Overweight (Without Type 2 Diabetes) With Weight-related Comorbidities
Conditions
Keywords
Tirzepatide, LY3298176, dual incretin, GIP, GLP-1, obesity, overweight, weight management, placebo, randomized, double-blind, once-weekly, subcutaneous, lifestyle intervention
Brief summary
This Phase 3 study evaluates the efficacy and safety of once-weekly subcutaneous tirzepatide (a dual GIP and GLP-1 receptor agonist) at 5 mg, 10 mg, or 15 mg versus placebo, each used with a reduced-calorie diet and increased physical activity, in adults without type 2 diabetes who have obesity or are overweight with weight-related comorbidities. The primary efficacy assessment is at Week 72. Participants with prediabetes at randomization may continue in an additional long-term treatment period to assess progression to type 2 diabetes and longer-term weight outcomes.
Detailed description
After screening, eligible participants are randomized in a 1:1:1:1 ratio to receive tirzepatide 5 mg, 10 mg, 15 mg, or placebo once weekly by subcutaneous injection using an autoinjector. All participants receive lifestyle counseling focused on a reduced-calorie diet and increased physical activity. The main treatment period is 72 weeks. Participants identified with prediabetes at randomization can continue study treatment for up to 176 weeks (plus follow-up), allowing evaluation of longer-term weight management and time to onset/progression to type 2 diabetes. Safety is monitored throughout, including adverse events and laboratory testing.
Interventions
DRUGTirzepatide
(once-weekly SC injection; doses 5/10/15 mg)
DRUGPlacebo
(once-weekly SC injection)
BEHAVIORALReduced-calorie diet
increased physical activity counseling
Sponsors
Hudson Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants and investigators are blinded to treatment assignment. Study drug and placebo are administered using similar autoinjector pens; randomization and drug dispensing are managed centrally via an interactive system.
Intervention model description
Parallel group, 4-arm study. Participants randomized 1:1:1:1 to tirzepatide 5 mg, 10 mg, 15 mg, or placebo once weekly, plus lifestyle intervention. Main evaluation at 72 weeks; participants with prediabetes may continue treatment up to 176 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* BMI ≥30 kg/m², OR BMI ≥27 kg/m² with ≥1 weight-related comorbidity (e.g., hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease) * History of at least one unsuccessful dietary effort to lose weight (self-reported) * Investigator judges participant capable and willing to self-inject (or have assistance), follow lifestyle advice, maintain a diary, and complete questionnaires * Age ≥18 years * Meets protocol contraception/pregnancy criteria (as applicable) and provides written informed consent
Exclusion criteria
* Type 1 or type 2 diabetes, history of ketoacidosis/hyperosmolar state, or screening labs diagnostic of diabetes * Recent significant weight change (\>5 kg within 3 months prior to screening) * Prior/planned bariatric surgery; recent/ongoing endoscopic or device-based obesity therapies * Severe renal impairment (eGFR \<30 mL/min/1.73 m²) * Clinically significant gastric emptying abnormality or chronic use of drugs that directly affect GI motility * History of chronic or acute pancreatitis * Clinically significant thyroid abnormalities at screening (e.g., TSH outside protocol range) or anticipated need to initiate thyroid replacement during study * Obesity due to other endocrinologic disorders (e.g., Cushing syndrome) or monogenic/syndromic obesity (e.g., MC4R deficiency, Prader-Willi syndrome) * Significant unstable major depressive disorder/severe psychiatric disorder, lifetime suicide attempt, or concerning suicidality screening (PHQ-9/C-SSRS criteria) * Uncontrolled hypertension; recent major cardiovascular events; NYHA class IV heart failure * Active or significant liver disease or certain elevated liver tests at screening (per protocol thresholds) * Elevated calcitonin above protocol thresholds; personal/family history of medullary thyroid carcinoma or MEN2 * Active/untreated malignancy or remission \<5 years (with specified exceptions) * Any other condition contraindicating GLP-1 receptor agonist therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean percent change in body weight from randomization | 72 Weeks |
| Percentage of participants achieving ≥5% body weight reduction from randomization | 72 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change in body weight | 72 Weeks | Mean change in body weight (kg) from randomization (pooled 10 mg and 15mg vs placebo) |
| Changes in cardiometabolic measures in triglycerides | 72 weeks | — |
Countries
China
Contacts
CONTACTSeni S Lu, Phd
Outcome results
None listed