The main purpose of this study is to investigate the safety and tolerability of the study drug LY3457263 in healthy participants and participants with type 2 diabetes. Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. The study has two parts (part A and B). Each part will last up to 10 weeks and may include up to either 13 (part A) or 19 (part B) visits.

Inclusion Criteria:

• Males that agree to use an effective method of contraception or agree to remain abstinent

• Females that are not of childbearing potential due to postmenopausal status or due to surgical sterility

• Part A only:

  • Are overtly healthy
  • Body mass index (BMI) of 18.5 to 35 kilograms per meter squared (kg/m²)

• Part B only:

  • Have been diagnosed with Type 2 Diabetes (T2D) for at least 6 months prior to screening
  • Be treated for T2D with stable dose of metformin, a stable dose of a dipeptidyl peptidase-4 (DPP-4) inhibitor with or without metformin, or a stable dose of a glucagon-like peptide-1 (GLP-1) receptor agonist with or without metformin for at least 3 months prior to screening
  • BMI of 27 to 40 kg/m²

Exclusion Criteria:

• Have undergone any form of bariatric surgery

  • Have used or intend to use medications that promote weight loss within 3 months prior to screening, for the duration of the study

  • Part A only:

    • Have fasting plasma glucose (PG) levels ≥7 millimoles per liter (mmol/L) (≥126 milligrams per deciliter (mg/dL)) at screening
    • Have Hemoglobin A1c (HbA1c) level ≥ 6.5% (48 millimoles per mole (mmol/mol)) at screening
    • Have serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >20% and 10%, above the upper limit of normal (ULN), respectively. Elevation of total bilirubin level is considered acceptable in case of Gilbert's disease (with a normal direct bilirubin)

  • Part B only:

    • Have Type 1 Diabetes or latent autoimmune diabetes in adults
    • Have uncontrolled diabetes defined as an episode of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to screening
    • Have known proliferative diabetic retinopathy, diabetic maculopathy, or severe nonproliferative diabetic retinopathy
    • Present comorbid conditions commonly associated with diabetes (for example, hypertension, hypercholesterolemia, hypothyroidism) unless they are well-controlled with stable medication
    • Have had an episode of severe hypoglycaemia within 6 months prior to screening, or have a history of hypoglycaemia unawareness or poor recognition of hypoglycaemia
    • Have a history of acute or chronic pancreatitis or elevation in serum lipase and/or amylase >2 × ULN at screening
    • Have a resting heart rate of <50 or >100 beats per minute
    • Have an estimated glomerular filtration rate (<60 milliliter/minute (mL/min)/1.73 m2, or a level of estimated glomerular filtration rate that would contraindicate the use of metformin per the label in the respective country
    • Have a screening calcitonin ≥20.0 picograms per milliliter (pg/mL)
    • Fasting serum triglyceride level of >500 mg/dL at screening
    • Have serum AST or ALT >3 × ULN or TBL >1.5 × ULN (except for participants diagnosed with Gilbert's syndrome)
    • Have taken any prescription medication that are specifically indicated for lowering serum triglycerides within the last 3 months
    • Have taken within the last 3 months any medications that interfere with absorption of dietary cholesterol or fats
    • Use of medications known to prolong the QT/QTc interval
    • Treated only with diet and exercise at study entry