The GZPL master protocol will support 2 independent studies, J2A-MC-GZL1 (GZL1) and J2A-MC-GZL2 (GZL2). The purpose of this study is to create a framework to evaluate the safety and efficacy of orforglipron for the treatment of hypertension in participants with obesity or overweight.

Inclusion Criteria:

• Has systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg (if DBP criteria alone is met, SBP must be ≥130 mmHg) at screening (Visit 1).
• Has SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg (if DBP criteria alone is met, SBP must be ≥130 mmHg) at week 0 (Visit 3).
• Untreated for hypertension, or on stable antihypertensive medications ≥ 30 days prior to Visit 1.
• Have a body mass index (BMI) ≥ 25 kg/m².

Exclusion Criteria:

• Has SBP ≥170 mmHg and/or DBP ≥110 mmHg at Visit 1 or at Visit 3.

• Has known secondary causes of hypertension

• Have heart failure with reduced ejection fraction (HFrEF) diagnosis

• Have had any of the following conditions within 90 days prior to screening.

  • hospitalization for hypertension or for congestive heart failure
  • acute coronary syndrome or acute myocardial infarction, or
  • cerebrovascular accident (stroke).

• Have type 1 diabetes (T1D)

• Have acute or chronic hepatitis, including a history of autoimmune hepatitis

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 and approval of the indication studied in the US and European Union (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.