A Study of LY3493269 in Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The main purpose of this study is to determine the side effects related to LY3493269 in participants with type 2 diabetes. Blood tests will be performed to check concentrations of LY3493269 in the bloodstream. Each enrolled participant will receive LY3493269, dulaglutide, or placebo. The study will last up to approximately 16 weeks for each participant and may include up to 11 visits.

Official Title
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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple-Ascending Subcutaneous Doses of LY3493269 in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: LY3493269
* Drug: Dulaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are male or female not of childbearing potential Have a body mass index of 23 to 50 kilograms per square meter (kg/m²), inclusive, at screening Have had a stable body weight (<5% body weight change) for the 3 months prior to screening Have not modified their diet or adopted any nutritional lifestyle modification in the 3 months prior to screening Have type 2 diabetes mellitus (T2DM) controlled with diet and exercise alone or are on a stable dose of metformin for at least 3 months before screening. Patients with comorbid conditions commonly associated with diabetes (for example, hypertension, hypercholesterolemia, hypothyroidism) may be eligible for inclusion if conditions are assessed by the investigator to be well controlled and stable for at least 3 months prior to screening Have an HbA1c of at least 7.0% and no more than 10.5% at screening Have clinical laboratory test results within the normal range for the population or investigative site, or with abnormalities deemed not clinically significant by the investigator Exclusion Criteria: Have type 1 diabetes mellitus or latent autoimmune diabetes in adults Have uncontrolled diabetes, defined as an episode of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to screening Have a history of proliferative diabetic retinopathy, diabetic maculopathy, or severe nonproliferative diabetic retinopathy that requires acute treatment Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before screening or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms. Have a definitive diagnosis of autonomic neuropathy as evidenced by urinary retention, resting tachycardia, orthostatic hypotension, or diabetic diarrhea Have a history of acute or chronic pancreatitis Have a self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or medullary thyroid carcinoma Have calcitonin levels of 20 picograms per millilitre (pg/mL) or more at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3493269<br>LY3493269 administered Subcutaneous (SC). | Drug: LY3493269<br>* Administered SC<br>|
| Active Comparator: Dulaglutide<br>Dulaglutide administered SC. | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|
| Placebo Comparator: Placebo<br>Placebo administered SC. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of SAEs, TEAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Baseline through final follow-up at Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3493269 | PK: AUC of LY3493269 | Baseline through final follow-up at Day 57 | 
| PK: Maximum Concentration (Cmax) of LY3493269 | PK: Cmax of LY3493269 | Baseline through final follow-up at Day 57 | 
| Pharmacodynamics (PD):Change from baseline to Day 29 in Fasting Glucose (FG) |  | Baseline, Day 29 |