A Study to Investigate Weight Management With LY3841136 and Tirzepatide (LY3298176), Alone or in Combination, in Adult Participants With Obesity or Overweight With Type 2 Diabetes

A Phase 2, Parallel-Group, Double-Blind, Placebo-Controlled Study to Investigate Weight Management With LY3841136 and Tirzepatide, Alone or in Combination, in Adult Participants With Obesity or Overweight With Type 2 Diabetes

The main purpose of this study, performed under the master protocol W8M-MC-CWMM (NCT06143956), is to investigate the safety and efficacy of LY3841136 for chronic weight management alone or in combination with Tirzepatide across a wide dose range in participants with Type 2 Diabetes. Participation in the study will last about 64 weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo; Drug: LY3841136

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1120AAC
    • Centro Médico Viamonte
  • Buenos Aires, Argentina, C1056ABI
    • Centro de Investigaciones Metabólicas (CINME)
  • Buenos Aires, Argentina, C1405BUB
    • Consultorio de Investigacion Clinica EMO SRL
  • Buenos Aires, Argentina, C1425AGC
    • Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
      • The Institute for Liver Health II dba Arizona Clinical Trials - Mesa
    • Phoenix, Arizona, United States, 85032
      • Hope Research Institute
    • Scottsdale, Arizona, United States, 85260
      • Headlands Research - Scottsdale
    • Tucson, Arizona, United States, 85712
      • The Institute for Liver Health II dba Arizona Liver Health-Tucson
  • California
    • Greenbrae, California, United States, 94904
      • NorCal Medical Research, Inc
    • Huntington Park, California, United States, 90255
      • Velocity Clinical Research, Huntington Park
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
  • Florida
    • Fleming Island, Florida, United States, 32003
      • Northeast Research Institute (NERI)
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc
    • Miami, Florida, United States, 33165
      • New Horizon Research Center
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Orlando, Florida, United States, 32803
      • Charter Research - Winter Park
    • The Villages, Florida, United States, 32162
      • Charter Research - Lady Lake
  • Idaho
    • Ammon, Idaho, United States, 83406
      • Medical Research Partners
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials - Andersonville
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials - Ravenswood
    • Skokie, Illinois, United States, 60077
      • Northshore University Health System
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Iowa Diabetes and Endocrinology Research Center
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Diabetes & Endocrinology
  • Massachusetts
    • Needham, Massachusetts, United States, 02492
      • Knownwell
    • New Bedford, Massachusetts, United States, 02740
      • Lucida Clinical Trials
  • Michigan
    • Southfield, Michigan, United States, 48034
      • Headlands Research - Detroit
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
    • Springfield, Missouri, United States, 65807
      • Clinvest Headlands Llc
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Las Vegas Medical Research
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • East Syracuse, New York, United States, 13057
      • Velocity Clinical Research, Syracuse
    • Port Jefferson Station, New York, United States, 11776
      • North Suffolk Neurology
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, LLC
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Medication Management
    • Monroe, North Carolina, United States, 28112
      • Monroe Biomedical Research
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research, Inc
    • New Bern, North Carolina, United States, 28562
      • Lucas Research, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research, LLC
  • Tennessee
    • Nashville, Tennessee, United States, 37211
      • Quality Medical Research
  • Texas
    • Austin, Texas, United States, 78745
      • IMA Clinical Research Austin
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research, Dallas
    • Dallas, Texas, United States, 75251
      • FutureSearch Trials of Dallas
    • Houston, Texas, United States, 77079
      • PlanIt Research, PLLC
    • San Antonio, Texas, United States, 78240
      • Endeavor Clinical Trials
    • San Antonio, Texas, United States, 78229
      • Tekton Research - Fredericksburg Road
    • Weslaco, Texas, United States, 78596
      • Texas Valley Clinical Research
  • Virginia
    • Danville, Virginia, United States, 24541
      • Spectrum Medical, Inc.
  • Washington
    • Wenatchee, Washington, United States, 98801
      • Central Washington Health Services Association d/b/a Confluence Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

W8M-MC-LAA2

• Have a Body Mass Index (BMI) of ≥27 kilograms per square meter (kg/m²)
• Have Type 2 Diabetes
• Have a HbA1c ≥7.0 % (53 millimoles/mole (mmol/mol)) to ≤10.5% (91 mmol/mol) and treated with diet and exercise alone or with a stable dose of metformin (and not more than the locally approved dose) with or without a sodium-glucose cotransporter 2 (SGLT2) inhibitor for at least 3 months prior to screening

W8M-MC-CWMM:

• Have had a stable body weight for the 3 months prior to randomization (<5% body weight gain and/or loss)

Exclusion Criteria:

W8M-MC-LAA2

• Have a history of severe hypoglycemia or hypoglycemia unawareness within the last 6 months prior to screening
• Have an on-going or history of bradyarrhythmia and/or sinus bradycardia
• Have an elevated resting pulse rate (mean >100 beats per minute (bpm)) or reduced resting pulse rate (mean <60 bpm) at screening

• Have any of the following cardiovascular conditions within 6 months prior to screening:

  • acute myocardial infarction
  • cerebrovascular accident (stroke)
  • unstable angina, or
  • hospitalization due to congestive heart failure
• Have renal impairment measured as estimated glomerular filtration rate (eGFR) <45 milliliters per minute (mL/min)/1.73 m2
• Have a history of acute or chronic pancreatitis
• Have fasting triglycerides >500 milligrams per deciliter (mg/dL) (5.7 mmol/L) at screening
• All concomitant medications should be at a stable dose for at least 3 months prior to screening

W8M-MC-CWMM

• Have a prior or planned surgical treatment for obesity, except prior liposuction or abdominoplasty, if performed >1 year prior to screening.
• Have type 1 diabetes mellitus, latent autoimmune diabetes in adults, or history of ketoacidosis or hyperosmolar coma.
• Have poorly controlled hypertension.
• Have a history of symptomatic gallbladder disease within the past 2 years
• Have signs and symptoms of any liver disease other than nonalcoholic fatty liver disease.
• Have a lifetime history of suicide attempts.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo administered SC.	Drug: Placebo; Administered SC
Experimental: LY3841136 Dose 1; Participants will receive LY3841136 subcutaneously (SC)	Drug: LY3841136; Administered SC
Experimental: LY3841136 Dose 2; Participants will receive LY3841136 SC	Drug: LY3841136; Administered SC
Experimental: LY3841136 Dose 3; Participants will receive LY3841136 SC	Drug: LY3841136; Administered SC
Experimental: LY3841136 Dose 1 + Tirzepatide Dose 1; Participants will receive LY3841136 SC and Tirzepatide SC	Drug: Tirzepatide; Administered SC; Drug: LY3841136; Administered SC
Experimental: LY3841136 Dose 2 + Tirzepatide Dose 1; Participants will receive LY3841136 SC and Tirzepatide SC	Drug: Tirzepatide; Administered SC; Drug: LY3841136; Administered SC
Experimental: LY3841136 Dose 2 + Tirzepatide Dose 2; Participants will receive LY3841136 SC and Tirzepatide SC	Drug: Tirzepatide; Administered SC; Drug: LY3841136; Administered SC
Experimental: LY3841136 Dose 3 + Tirzepatide Dose 3; Participants will receive LY3841136 SC and Tirzepatide SC	Drug: Tirzepatide; Administered SC; Drug: LY3841136; Administered SC
Active Comparator: Tirzepatide Dose 3; Participants will receive Tirzepatide SC	Drug: Tirzepatide; Administered SC
Experimental: LY3841136 Dose 2 + Tirzepatide Dose 3; Participants will receive LY3841136 SC and Tirzepatide SC	Drug: Tirzepatide; Administered SC; Drug: LY3841136; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Body Weight	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Who Achieve ≥5% Body Weight Reduction	Week 48
Percentage of Participants Who Achieve ≥10% Body Weight Reduction	Week 48
Change from Baseline in Body Weight	Baseline, Week 48
Change from baseline in Hemoglobin A1c (HbA1c)	Baseline, Week 48
Pharmacokinetics (PK): Area Under the Curve (AUC) of LY3841136	Baseline, Week 48
PK: Maximum Concentration (Cmax) of LY3841136	Baseline, Week 48

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 to Investigate Weight Management With LY3841136 and Tirzepatide (LY3298176), Alone or in Combination, in Adult Participants With Obesity or Overweight With Type 2 Diabetes

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: September 17, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Type 2 Diabetes
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus, Type 2; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: 18809; W8M-MC-LAA2 (Other Identifier: Eli Lilly and Company); W8M-MC-CWMM Master Protocol (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No