A Study of LY3437943 in Participants With Type 2 Diabetes Mellitus (T2DM)

Study Overview
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Brief Summary
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The main purpose of this study is to learn about the side effects of LY3437943 when given to participants with type 2 diabetes. Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. Each enrolled participant will receive injections of LY3437943, dulaglutide, or placebo given just under the skin. For each participant, the study will last up to about 5 months and will include 16 visits to the study center.

Official Title
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A Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3437943 in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: LY3437943
* Drug: Dulaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have T2DM for at least 3 months before screening and are without advanced known possible complications of diabetes mellitus Have a glycated hemoglobin (HbA1c) value at lead-in and screening of ≥7.0% and ≤10.5% and treated with diet and exercise alone or a stable dose of metformin for at least 3 months prior to screening Have had a stable body weight for the 3 months prior to randomization (<5% body weight change) Have a body mass index of 23 to 50 kilograms per square meter (kg/m²), inclusive Male participants agree to use an effective method of contraception for the duration of the study plus 90 days, which corresponds to 4 months after the last investigational product dose Women not of childbearing potential may participate and include those who are: infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as mullerian agenesis; or those who are postmenopausal 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 known clinically significant gastric emptying abnormality Have had an episode of severe hypoglycemia Have a history of acute or chronic pancreatitis or fasting serum triglyceride level of >500 milligrams per deciliter (mg/dL) at screening and/or Day-2. If participant is on lipid-lowering therapies, doses must be stable for 30 days prior to screening Have known liver disease, obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or have elevations in aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) greater than 3X upper limit of normal (ULN) at screening and/or Day -2

Ages Eligible for Study
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Minimum Age: 20 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: LY3437943<br>LY3437943 administered subcutaneously (SC) | Drug: LY3437943<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 Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Baseline through Day 106 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve of LY3437943 | PK: AUC of LY3437943 | Baseline through study completion (12 weeks) | 
| PK: Maximum Concentration (Cmax) of LY3437943 | PK: Cmax of LY3437943 | Baseline through study completion (12 weeks) | 
| Change from Baseline in Mean Daily Plasma Glucose (PG) | Change from baseline in mean daily PG from 6-point PG profile | Baseline through Day 80 |