A Study of LY4057996 in Healthy Participants and Participants With Type 1 and Type 2 Diabetes

NCT06945406 | Recruiting Phase 1

• 3 other identifiers: 273292024-519151-28-00J6B-MC-YKAA
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate how well LY4057996 is tolerated and what side effects may occur in healthy participants and participants with Type 1 and Type 2 Diabetes. The study drug will be administered either subcutaneously (SC) (under the skin) or intravenously (IV) (into a vein in the arm). Blood tests will be performed to check how much LY4057996 gets into the bloodstream and how long it takes the body to eliminate it. The study will last 11 weeks for Part A1-A2, 4 weeks for A3-A5, 6 weeks for Part B and 7 weeks for Part C, all approximations, excluding a screening period.

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Number of Participants with One or More Serious Adverse Event(s) (SAEs) and Adverse Event(s) (AEs) Considered by the Investigator to be Related to Study Drug Administration

  A summary of SAEs and AEs regardless of causality, will be reported in the Reported Adverse Events module

  Baseline to Study Completion (Up to 47 Weeks)

Secondary Outcomes (4)

• Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY4057996

  Baseline to Study Completion (Up to 47 Weeks)

• PK: Maximum Concentration (Cmax) of LY4057996

  Baseline to Study Completion (Up to 47 Weeks)

• Pharmacodynamic (PD): Change from Baseline in Fasting Glucose

  Baseline to Study Completion (Up to 47 Weeks)

• PD: AUC of Glucose Infusion Rate (GIR)

  Baseline Up to 10 weeks

Study Arms (6)

LY4057996 Part A (Cohorts A1-A5)

EXPERIMENTAL

LY4057996 administered subcutaneously (SC) and/or intravenously (IV)

Drug: LY4057996 SC; Drug: LY4057996 IV

Placebo Part A (Cohort A1-A5)

PLACEBO COMPARATOR

Placebo administered SC and/or IV

Drug: Placebo SC; Drug: Placebo IV

LY4057996 Part B

EXPERIMENTAL

LY4057996 administered SC

Drug: LY4057996 SC

LY4057996 Part C

EXPERIMENTAL

LY4057996 and interventions of pre-study basal insulin and Lispro administered SC

Drug: LY4057996 SC; Drug: Lispro SC; Drug: Pre-study basal insulin SC

Degludec Part A (Cohort A2-A5)

ACTIVE COMPARATOR

Degludec administered SC and/or IV

Drug: Degludec SC; Drug: Degludec IV

Degludec Part B

ACTIVE COMPARATOR

Degludec administered SC

Drug: Degludec SC

Interventions

LY4057996 SC DRUG

Administered SC

LY4057996 Part A (Cohorts A1-A5); LY4057996 Part B; LY4057996 Part C

LY4057996 IV DRUG

Administered IV

LY4057996 Part A (Cohorts A1-A5)

Placebo SC DRUG

Administered SC

Placebo Part A (Cohort A1-A5)

Placebo IV DRUG

Administered IV

Placebo Part A (Cohort A1-A5)

Degludec SC DRUG

Administered SC

Degludec Part A (Cohort A2-A5); Degludec Part B

Lispro SC DRUG

Administered SC

LY4057996 Part C

Degludec IV DRUG

Administered IV

Degludec Part A (Cohort A2-A5)

Pre-study basal insulin SC DRUG

Administered SC

LY4057996 Part C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A for Healthy Participants:
• Are overtly healthy as determined by medical evaluation, including medical history, physical exam, laboratory tests, and cardiac screening assessment
• Part A for Type 2 Diabetes (T2DM) Participants:
• Are participants with T2DM diagnosed greater than 1 year before enrollment,
• On basal insulin therapy, insulin glargine, insulin detemir, or insulin degludec, greater than 10 units per day for at least 6 months (for Cohort 5 only)
• Glycated hemoglobin (HbA1c) 6.5% to 9.5% inclusive at screening
• Part B
• Have Type 1 Diabetes (T1D) for at least 1 year with a fasting C-peptide level of 0.20 nanomole per liter (nmol/L) or less or non-fasting C-peptide level of 0.30 nmol/L or less at screening
• HbA1c 6% to 8.5% inclusive at screening
• Part C
• Have T1D for at least 1 year with a fasting C-peptide level of 0.20 nanomole per liter (nmol/L) or less or non-fasting C-peptide level of 0.30 nmol/L or less at screening
• HbA1c 6 to 8.5% inclusive at screening
• All Parts
• Have blood pressure of less than 140/90 millimeters of mercury (mmHg) for healthy participants or 150/90 mmHg for participants with diabetes and pulse rate of less than 90 beats per minute (bpm) (supine)
• No hypoglycemia unawareness for all Type 1 and Type 2 Diabetes participants

You may not qualify if:

• Have had more than 1 emergency room visit or hospitalization due to poor glucose control (hyperglycemia or diabetic ketoacidosis) within 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 6 months prior to screening
• All Parts
• Cardiovascular: no significant history of cardiovascular disease (CVD)
• Gastrointestinal: have gastroparesis or have undergone gastric surgery
• Hepatic: have acute or chronic hepatitis

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Profil Institut für Stoffwechselforschung

Neuss, 41460, Germany

RECRUITING

Related Links

• A Study of LY4057996 in Healthy Participants and Participants With Type 1 and Type 2 Diabetes

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Part A is Double-Blinded, Parts B and C are Open-Label
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parts A and C are sequential: Parts B and C are crossover

Study Record Dates

• First Submitted: April 18, 2025
• First Posted: April 25, 2025
• Study Start: May 16, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)