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

A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY4057996 in Healthy Participants and Participants With Type 1 and Type 2 Diabetes

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Placebo IV; Drug: Placebo SC; Drug: LY4057996 SC; Drug: LY4057996 IV; Drug: Lispro SC; Drug: Pre-study basal insulin SC; Drug: Degludec SC; Drug: Degludec IV

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: LillyTrials@Lilly.com
• Study Contact Backup: Name: Physicians interested in becoming principal investigators please contact; Email: clinical_inquiry_hub@lilly.com

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Recruiting
    • Profil Institut für Stoffwechselforschung
    • Principal Investigator: Oliver Klein
    • Contact: Phone Number: +49 (0) 2131 4018 180

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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, 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

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), 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY4057996 Part A (Cohorts A1-A5); LY4057996 administered subcutaneously (SC) and/or intravenously (IV)	Drug: LY4057996 SC; Administered SC; Drug: LY4057996 IV; Administered IV
Placebo Comparator: Placebo Part A (Cohort A1-A5); Placebo administered SC and/or IV	Drug: Placebo IV; Administered IV; Drug: Placebo SC; Administered SC
Experimental: LY4057996 Part B; LY4057996 administered SC	Drug: LY4057996 SC; Administered SC
Experimental: LY4057996 Part C; LY4057996 and interventions of pre-study basal insulin and Lispro administered SC	Drug: LY4057996 SC; Administered SC; Drug: Lispro SC; Administered SC; Drug: Pre-study basal insulin SC; Administered SC
Active Comparator: Degludec Part A (Cohort A2-A5); Degludec administered SC and/or IV	Drug: Degludec SC; Administered SC; Drug: Degludec IV; Administered IV
Active Comparator: Degludec Part B; Degludec administered SC	Drug: Degludec SC; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 18, 2025
• First Submitted That Met QC Criteria: April 18, 2025
• First Posted (Actual): April 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Hypoglycemic Agents; Insulin, Long-Acting
• Other Study ID Numbers: 27329; 2024-519151-28-00 (Ctis); J6B-MC-YKAA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes