The main purpose of this study is to determine the safety and efficacy of orforglipron. Participants will have Type 2 Diabetes (T2D) and have inadequate glycemic control with insulin glargine with or without metformin and/or SGLT-2 (sodium-glucose cotransporter-2) inhibitor. The study will last about 46 weeks and may include up to 20 visits.

Inclusion Criteria:

• Have Type 2 Diabetes (T2D)

• Have HbA1c ≥7.0% [53 mmol/mol] to ≤10.5% [91 mmol/mol]

• Have been treated with stable doses of the same formulation of the following for ≥90 days prior to screening visit 1 and have maintained the same doses through randomization:

  • insulin glargine U-100 (100 U/mL) ≥0.25 U/kg/QD (units per kilogram per day) or ≥20 U/QD alone, or
  • insulin glargine U-100 (100 U/mL) ≥0.25 U/kg/QD or ≥20 U/QD in combination with
  • metformin, or
  • SGLT-2 inhibitor, or
  • both metformin and SGLT-2 inhibitor.

• Are of stable body weight (±5%) for at least 90 days prior to screening visit 1 and agree to not initiate an intensive diet or exercise program during the study with the intent of reducing body weight, other than the lifestyle and/or dietary measures for diabetes treatment.

• Have a Body Mass Index (BMI) ≥23.0 kg/m^2 at baseline.

Exclusion Criteria:

• Have New York Heart Association functional classification III-IV congestive heart failure.

• Have had any of the following cardiovascular conditions within 60 days prior to baseline.

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

• Have acute or chronic hepatitis, including a history of autoimmune hepatitis, signs or symptoms of any other liver disease other than nonalcoholic fatty liver disease

• Have had chronic or acute pancreatitis any time.

Anonymized individual participant 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.