Inclusion Criteria:

1. Body mass index (BMI) ≥ 28.0 kg/m^2;
2. The target knee must meet the diagnostic criteria of American College of Rheumatology (ACR) for knee osteoarthritis (clinical and radiological), with moderate radiographic changes (Kellgren-Lawrence grade 2 or 3). The target knee is defined as the knee with the most symptomatic knee at screening period; if pain in both knees are equal, the target knee will be the most dominant leg (preferred leg);
3. Prior to screening, target knee pain lasting more than 12 weeks, and according to participant's self-report or medical history at screening, target knee pain lasting more than 15 days in the past month;
4. At screening and prior to randomization, WOMAC pain score (NRS 0-10) of the target knee must be between 4 and 9 (to avoid bias in reporting, participants must not be informed of the pain score used to determine eligibility for the study);
5. Self-reported by the participant who has a history of unsuccessful weight loss attempt by diet and exercise.

Exclusion Criteria:

1. The target knee has undergone joint replacement surgery;

2. The target knee has undergone arthroscopy within 12 months prior to screening;

3. At the time of screening, the target knee joint has any clinical features and symptoms of other active infections or crystal-induced arthropathies, as well as any other active joint diseases that may interfere with assessment;

4. The target knee has received intra-articular injections of hyaluronic acid, any other investigational drugs, or biologics within 3 months prior to screening; or has undergone any procedures that result in persistent sensory loss in the target knee (e.g., ablation) within 6 months prior to screening;

5. Has received any intramuscular or oral corticosteroids (investigational or marketed) within 30 days prior to screening, or has received any intra-articular corticosteroid injections (investigational or marketed) in any joint within 90 days prior to screening;

6. History of joint instability in either knee within 12 months prior to screening, such as anterior cruciate ligament rupture or recent trauma;

7. History of any other potentially causative and/or confounding diseases, including Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease-associated arthritis, sarcoidosis, amyloidosis, or fibromyalgia;

8. Presence of symptomatic hip osteoarthritis at the time of screening, with the exception of those who have undergone hip replacement surgery;

9. Conditions that may interfere with the assessment of target knee pain during screening include, but are not limited to:

   • Pain in any part of the lower limb or back equal to or more severe than the pain in the target knee;
   • Pain radiating to the knee from other areas, such as hip pain affecting the knee or radicular pain;
   • Chronic widespread pain (including neuropathic pain);

10. Change of body weight >5% within 3 months prior to screening (selfreported);

11. Diagnosis of diabetes (excluding gestational diabetes), or with a history of diabetic ketoacidosis or hyperosmolar state/coma