A Study of LY3493269 in Participants With Type 2 Diabetes

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Dulaglutide; Drug: LY3493269

• Study Type: Interventional
• Enrollment (Actual): 56
• 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
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1.5 milligrams (mg) Dulaglutide; Participants received 1.5 mg dulaglutide subcutaneously (SC) once weekly (QW) for 4 weeks.	Drug: Dulaglutide; Administered SC; Other Names: LY2189265
Experimental: 0.3 mg LY3493269; Participants received 4 fixed dosed of 0.3 mg LY3493269 SC QW for 4 weeks.	Drug: LY3493269; Administered SC
Experimental: 1 mg LY3493269; Participants received 4 fixed dosed of 1 mg LY3493269 SC QW for 4 weeks.	Drug: LY3493269; Administered SC
Experimental: 0.75/1.5/3 mg LY3493269; Participants received LY3493269 0.75 mg on week 1, 1.5 mg on week 2 and 3 mg on week 3 and 4 SC as weekly doses.	Drug: LY3493269; Administered SC
Experimental: 1.5/3/4/5 mg LY3493269; Participants received LY3493269 1.5 mg on week 1, 3 mg on week 2, 4 mg on week 3 and 5 mg on week 4 as weekly doses.	Drug: LY3493269; Administered SC
Placebo Comparator: Placebo; Participants received placebo subcutaneously (SC) once weekly (QW) for 4 weeks.	Drug: Placebo; Administered SC

What is the study measuring?

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	TEAE is an untoward medical occurrence that emerges during a defined treatment period, having been absent pretreatment, or worsens relative to the pretreatment state, and does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence that, at any dose: Results in death; Is life-threatening; Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent disability/incapacity; Is a congenital anomaly/birth defect; Other situations: Based on medical or scientific judgement. 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 From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269	Area Under the Concentration Versus Time Curve from Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269	Predose, 6, 12, 24, 48, 72, 96 and 168 h postdose at Weeks 1 and 4.
PK: Maximum Observed Drug Concentration (Cmax) of LY3493269	Maximum Observed Drug Concentration (Cmax) of LY3493269	Predose, 6, 12, 24, 48, 72, 96 and 168 h postdose at Weeks 1 and 4.
Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose	Pharmacodynamics (PD): Summary Statistics (Mean, Standard Deviation) of Change From Baseline to Day 29.	Baseline, Day 29

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 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY3493269 in Participants With Type 2 Diabetes

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Actual): March 9, 2021
• Study Completion (Actual): March 9, 2021

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Dulaglutide
• Other Study ID Numbers: 17530; J1X-MC-GZHC (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: Yes
• Studies a U.S. FDA-regulated device product: No