The purpose of this study is to measure the change in hemoglobin A1c (HbA1c) with LY3457263 compared with placebo in participants with type 2 diabetes who are not at HbA1c goal when treated with a stable dose of semaglutide or tirzepatide. Participation in the study will last about 9 months.

Inclusion Criteria:

• Have type 2 diabetes

• Have HbA1c ≥7.5% to ≤10.5% at screening

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

• Have had a stable body weight for the three months prior to screening

• On stable treatment dose of one of the following incretins for at least three months prior to screening:

  • Injectable semaglutide (1 and 2 milligram (mg))
  • Injectable tirzepatide (5, 7.5, 10, 12.5 and 15 mg)

Exclusion Criteria:

• Have type 1 diabetes, latent autoimmune diabetes, or history of ketoacidosis or hyperosmolar coma

• Have a prior or planned surgical treatment for obesity

• Have any of the following cardiovascular conditions within three months prior to screening:

  • acute myocardial infarction
  • cerebrovascular accident (stroke)
  • unstable angina, or
  • hospitalization due to congestive heart failure

• Have used insulin to control blood glucose within the past year (short-term use allowed)

• Current use of prohibited oral antihyperglycemic medication (OAM) (including but not limited to, Dipeptidyl Peptidase IV Inhibitors (DPP-4i) and meglitinides) may be randomized if the prohibited OAM treatment was discontinued at least 3 months prior to screening

  • If participant has been on stable doses (for at least three months) of up to three permitted OAMs (limited to metformin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, alpha-glucosidase inhibitors, sulfonylurea, and/or thiazolidinediones (TZD), they are permitted to participate in the study

• Have taken any medications or alternative remedies for weight loss within three months prior to 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 and 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.