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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Dulaglutide; Drug: LY3437943

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
  • Florida
    • Miami, Florida, United States, 33143
      • Miami Research Associates
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • PRA International
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo administered SC	Drug: Placebo; Administered SC
EXPERIMENTAL: LY3437943; LY3437943 administered subcutaneously (SC)	Drug: LY3437943; Administered SC
ACTIVE_COMPARATOR: Dulaglutide; Dulaglutide administered SC	Drug: Dulaglutide; Administered SC; Other Names: LY2189265

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) 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
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
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)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Urva S, Coskun T, Loh MT, Du Y, Thomas MK, Gurbuz S, Haupt A, Benson CT, Hernandez-Illas M, D'Alessio DA, Milicevic Z. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet. 2022 Nov 26;400(10366):1869-1881. doi: 10.1016/S0140-6736(22)02033-5. Epub 2022 Oct 27.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2019
• Primary Completion (ACTUAL): December 28, 2020
• Study Completion (ACTUAL): December 28, 2020

Study Registration Dates

• First Submitted: October 28, 2019
• First Submitted That Met QC Criteria: October 28, 2019
• First Posted (ACTUAL): October 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 18, 2021
• Last Verified: January 15, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Dulaglutide
• Other Study ID Numbers: 17137; J1I-MC-GZBB (OTHER: 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: Yes
• Studies a U.S. FDA-regulated device product: No