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

Phase 1

Not yet recruiting

• Conditions: Healthy; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2
• Interventions: Drug: LY4057996 SC; Drug: Placebo SC; Drug: Degludec SC; Drug: LY4057996 IV; Drug: Placebo IV; Drug: Lispro SC; Drug: Degludec IV; Drug: Pre-study basal insulin SC

• Registration Number: NCT06945406
• Lead Sponsor: Eli Lilly and Company

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, 5 weeks for Part B and 7 weeks for Part C, all approximations, excluding a screening period.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-18
• Study First Submitted QC: 2025-04-18
• Study First Posted: 2025-04-25
• Last Update Submitted: 2025-04-29
• Study Start: 2025-05
• Last Update Posted: 2025-05-02
• Primary Completion: 2026-08
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

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, 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% 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

Exclusion Criteria

• 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) 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LY4057996 Part A (Cohorts A1-A5)	LY4057996 SC	LY4057996 administered subcutaneously (SC) and/or intravenously (IV)
LY4057996 Part A (Cohorts A1-A5)	LY4057996 IV	LY4057996 administered subcutaneously (SC) and/or intravenously (IV)
Placebo Part A (Cohort A1-A5)	Placebo SC	Placebo administered SC and/or IV
Placebo Part A (Cohort A1-A5)	Placebo IV	Placebo administered SC and/or IV
LY4057996 Part B	LY4057996 SC	LY4057996 administered SC
LY4057996 Part C	LY4057996 SC	LY4057996 and interventions of pre-study basal insulin and Lispro administered SC
LY4057996 Part C	Lispro SC	LY4057996 and interventions of pre-study basal insulin and Lispro administered SC
LY4057996 Part C	Pre-study basal insulin SC	LY4057996 and interventions of pre-study basal insulin and Lispro administered SC
Degludec Part A (Cohort A2-A5)	Degludec SC	Degludec administered SC and/or IV
Degludec Part A (Cohort A2-A5)	Degludec IV	Degludec administered SC and/or IV
Degludec Part B	Degludec SC	Degludec and Lispro administered SC
Degludec Part B	Lispro SC	Degludec and Lispro administered SC

Primary Outcome Measures

Name	Time	Method
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	Baseline to Study Completion (Up to 47 Weeks)	A summary of SAEs and AEs regardless of causality, will be reported in the Reported Adverse Events module

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY4057996	Baseline to Study Completion (Up to 47 Weeks)	PK: AUC of LY4057996
PK: Maximum Concentration (Cmax) of LY4057996	Baseline to Study Completion (Up to 47 Weeks)	PK: Cmax of LY4057996
Pharmacodynamic (PD): Change from Baseline in Fasting Glucose	Baseline to Study Completion (Up to 47 Weeks)	PD: Change from Baseline in Fasting Glucose
PD: AUC of Glucose Infusion Rate (GIR)	Baseline Up to 10 weeks	PD: AUC of GIR

Trial Locations

Locations (1)

Profil Institut für Stoffwechselforschung; 🇩🇪 Neuss, Nordrhein-Westfalen, Germany