A Study of LY3457263 in Healthy Participants and Participants With Type 2 Diabetes

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.


Eligibility Criteria:
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