A Study of LY3025876 in Participants With Diabetes

Phase 1

Completed

Brief Summary: The main purpose of this study is to assess the safety and tolerability of LY3025876 given alone (Part A) and in combination with liraglutide (Part B) in participants with type 2 diabetes mellitus (T2DM).

Detailed Description: This study will also evaluate how much of the study drug enters the blood stream and how long it takes for the body to remove the study drug. Information about any side effects that may occur will also be collected. Participants will continue their usual diet and exercise program and may remain on their physician-prescribed dose of metformin.

Each part of the study is expected to last 10 to 12 weeks on average, not including screening. Participants may only enroll in one part.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of type 2 diabetes mellitus (T2DM) as determined by the investigator, controlled with diet or exercise alone or on a stable dose of metformin for at least 30 days
Have a body mass index (BMI) greater than or equal to 23 and less than or equal to 45 kilograms per square meter (kg/m^2) at screening
Have a supine blood pressure reading at screening of between 90-160 millimeter of mercury (mmHg) (systolic) and 40-95 mmHg (diastolic)
Women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause

Exclusion Criteria

Have taken LY3025876 or investigational drugs like it (for example, other fibroblast growth factor-21 [FGF21]-related drugs) or have known allergies to these drugs
History or presence of bone disease (including osteoporosis or unhealed fractures)
Current active treatment of periodontal disease
Have had a significant change in weight, defined as a gain or loss of at least 4 kilogram (kg) (9 pounds) in the last 3 months
Have had greater than 1 episode of severe hypoglycemia within 6 months of screening that required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions or had a seizure or coma
Have known allergies or a history of intolerance to liraglutide, glucagon-like peptide 1 (GLP-1) analogues, or other related compounds
Have a history of acute or chronic pancreatitis
Have a personal or family history of medullary thyroid carcinoma or have multiple endocrine neoplasia syndrome type 2

Arm && Interventions

Group	Intervention	Description
LY3025876 + Liraglutide	LY3025876	Part B: 5.0 mg of LY3025876 and 1.8 mg liraglutide administered as separate QD SQ injections for up to 28 days, after titration of liraglutide over 2 weeks.
LY3025876 + Liraglutide	Liraglutide	Part B: 5.0 mg of LY3025876 and 1.8 mg liraglutide administered as separate QD SQ injections for up to 28 days, after titration of liraglutide over 2 weeks.
Placebo + Liraglutide	Placebo	Part B: Placebo doses matching LY3025876 and 1.8 mg liraglutide administered as separate QD SQ injections for up to 28 days, after titration of liraglutide over 2 weeks.
LY3025876	LY3025876	Part A: 0.5 milligram (mg), 1.5 mg, 5 mg, and 15 mg of LY3025876 administered as once daily (QD) subcutaneous (SQ) injections for up to 28 days.
Placebo	Placebo	Part B: Placebo matching LY3025876 administered as QD SQ injections for up to 28 days
Placebo + Liraglutide	Liraglutide	Part B: Placebo doses matching LY3025876 and 1.8 mg liraglutide administered as separate QD SQ injections for up to 28 days, after titration of liraglutide over 2 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Predose on Day 1 up to Day 56 in each Part	A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC[0-24]) of LY3025876	Predose and 0.5 hour(hr), 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, and 24 hr Postdose	AUC(0-24) of individual participants was calculated by equation Area Under Concentration (AUC)=Dose/CL, where the clearance (CL) was estimated using a population PK model.
PK: Maximum Concentration (Cmax) of LY3025876	Days 1 and 28: Predose and 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, and 24 hr Postdose
Part A and Part B: Immunogenicity: The Number of Participants With Anti-LY3025876 Antibodies	Predose on Day 7, 14, 28, 56, and 180
Pharmacodynamics (PD): Change From Baseline to Day 28 in Fasting Glucose	Baseline, Day 28	Least Squares Mean (LS) Mean change from baseline in fasting glucose was modeled using Mixed Effect Model Repeat Measurement (MMRM) analysis with fixed effects of baseline, treatment, day, treatment\*day interaction, and participant as a random effect.

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Cincinnati, Ohio, United States