Overview

The main purpose of this study is to look at the amount of the study drug LY3938577 that gets into the blood stream and how long it takes the body to get rid of it. At a later stage of this study (part B and C) the blood sugar lowering effect and the duration of action of LY3938577 will be evaluated compared to Insulin Degludec.

The study will also evaluate the safety and tolerability of LY3938577 and information about any side effects experienced will be collected.

The study will be conducted in four parts (A, B, C, and D). Healthy participants in Part A Period 1 will receive a single dose of LY3938577 or a placebo given via intravenous (IV) infusion. In Part A Period 2, participants will receive a single subcutaneous (SC) dose of either LY3938577 or placebo. Participants in Part B with Type 1 Diabetes Mellitus (T1DM) will receive single doses of either LY3938577 or Insulin Degludec given via IV infusion. Participants in Part C with Type 1 Diabetes Mellitus (T1DM) will receive two doses of either LY3938577 or Insulin Degludec administered SC. Participants in Part D with Type 1 Diabetes Mellitus (T1DM) will be evaluated in 2 periods, with Period 1 administered pre-study basal insulin and lispro mealtime insulin to establish insulin needs, and Period 2 administered lispro mealtime insulin and daily doses of LY3938577.

The study will last up to approximately 11 weeks for Part A, 10 weeks for Part B, 13 weeks for Part C, and 10 weeks for Part D , including screening period.

Eligibility

Inclusion Criteria:

Part A -

• Participants who are overtly healthy as determined by medical history and physical examination.

Parts B and C -

• Have Type 1 Diabetes Mellitus (T1DM) for at least 2 years with a fasting C-peptide level of 0.20 Nanomoles Per Liter (nmol/L) or less, or nonfasting C-peptide level of 0.30 nmol/L or less at screening.
• Have well-controlled HbA1c between 6.0% to 8.5 percent (%).
• Insulin pump users with a total daily basal dose between 15 to 45 International Unit (IU).

Part D -

• Have T1DM for at least 1 year with a fasting C-peptide level of 0.20 nmol/L or less, or non-fasting C-peptide level of 0.30 nmol/L or less.
• HbA1c between 6% to 8.5% inclusive.
• Insulin pump users with a total daily basal dose between 15 to 45 International Unit (IU).
• Insulin multiple daily injection users (glargine or degludec insulin) with a total daily insulin dose between 0.3 to \<1.2 (I)U/kg/day.
• No hypoglycaemia unawareness.
• Basal insulin dose that is between 30% to 70% of the total daily insulin dose
• Are able to complete the exercise challenge test.

All Parts -

• Have normal blood pressure, pulse rate and safety laboratory test results that are acceptable for the study.
• Have body mass index (BMI) between 18.0 and 35.0 kilograms per meter squared (kg/m²), inclusive, at screening.
• Have venous access sufficient to allow for blood sampling.
• Male and/or female not of childbearing potential.

Exclusion Criteria:

Parts B, C, and D -

• Have had more than 1 emergency room visit or hospitalization due to poor glucose control (hyperglycemia or diabetic ketoacidosis) within the last 6 months prior to screening.
• Have had any episodes of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia), hypoglycemia unawareness, or both within the last 6 months prior to screening.

Parts B and C -

• Have been treated with Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RA), Dipeptidyl Peptidase 4 (DPP4) inhibitor, Glucose-dependent Insulinotropic Polypeptide (GIP) agonists, Metformin, or Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors within the previous 3 months.
• Have received systemic or inhaled glucocorticoid therapy (excluding topical, intraarticular, and intraocular preparations) for more than 14 consecutive days within 4 weeks before screening.

Part D -

• Have been treated with Dipeptidyl peptidase-4 (DPP-IV) inhibitors, GLP-1 RA, GIP/GLP-1 RA, Metformin, Pramlintide, SGLT2 inhibitors, or Neutral Protamine Hagedorn (NPH) insulin within the previous 3 months.

All Parts -

• Have had any of the following cardiovascular conditions: acute myocardial infarction, New York Heart Association Class III or IV heart failure, or cerebrovascular accident (stroke).
• Have gastroparesis or have undergone gastric bypass (bariatric) surgery or restrictive bariatric surgery (for example, Lap-Band®) prior to screening.
• Have history of renal transplantation, currently receiving renal dialysis, have serum creatinine level of more than 2.00 milligrams per decilitre (mg/dL) or have an estimated glomerular filtration rate of less than 60.0 milliliters (mL) / minute /1.73 square meters.
• Have acute or chronic hepatitis, or obvious clinical signs or symptoms of any other liver disease except non-alcoholic fatty liver disease (that is, participants with non-alcoholic fatty liver disease are eligible for participation), and/or have elevated liver enzyme measurements, as determined by the local laboratory at screening and as indicated:
  • Total bilirubin (TBL) \>2 × the Upper Limit of Normal (ULN) in the absence of Gilbert's syndrome, or
  • Alanine aminotransferase (ALT) /serum glutamic pyruvic transaminase (SGPT) \>2.5 × ULN, or
  • Aspartate aminotransferase (AST) /serum glutamic oxaloacetic transaminase (SGOT) \>2.5 × ULN.