The GZPT master protocol will support two independent studies, J2A-MC-GZT1 and J2A-MC-GZT2. Each study will see how well and safely orforglipron works in people with obesity or overweight who have osteoarthritis (OA) of the knee with pain. Participation in the study will last about 74 weeks.

Inclusion Criteria:

• Have a body mass index (BMI) of 27 kilograms per square meter (kg/m2) or higher at screening

• Have tried at least once to lose weight through diet but were unsuccessful

• Have osteoarthritis of the knee and at least one of the following conditions:

  • Be over 50 years old
  • Have morning knee stiffness that lasts about 30 minutes
  • Have a crackling or grinding sound or feeling in the knee

Exclusion Criteria:

• Have gained or lost more than 11 pounds within 90 days prior to screening
• Have had a surgery for obesity or plan to have one in the next 18 months
• Have an active knee infection
• Have type 1 diabetes, type 2 diabetes, or any other type of diabetes
• Have had a recent heart condition or New York Heart Association Functional Classification Class IV congestive heart failure
• Have used any glucagon-like peptide-1 (GLP-1) receptor agonist medication within 180 days of screening

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication or approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.