A Study to Investigate Weight Management With Bimagrumab (LY3985863) and Tirzepatide (LY3298176), Alone or in Combination, in Adults With Obesity or Overweight

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study of Bimagrumab and Tirzepatide, Alone or in Combination, to Investigate the Efficacy and Safety in Adult Participants With Obesity or Overweight Without Type 2 Diabetes

The main purpose of this study is to evaluate the efficacy and safety of Bimagrumab and Tirzepatide, alone or in combination, in adults with obesity or overweight, with at least one obesity related comorbidity, without Type 2 Diabetes. The study will last about 70 weeks.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group, LLC
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates
  • California
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
    • Lake Worth, Florida, United States, 33461
      • Altus Research
    • Miami, Florida, United States, 33135
      • Suncoast Research Group
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials - Ravenswood
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • SKY Integrative Medical Center/SKYCRNG
  • Pennsylvania
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Keystone Clinical Studies
  • Washington
    • Redmond, Washington, United States, 98052
      • Eastside Research Associates
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have a BMI of

  • ≥30 kilograms per square meter (kg/m2) or

  • ≥27 kg/m2 and <30 kg/m2, with at least one of the following weight-related comorbidities:

    • Hypertension
    • Dyslipidemia
    • Cardiovascular disease
    • Obstructive sleep apnea
• Have had a stable body weight for the 3 months prior to randomization (<5% body weight gain and/or loss)

Exclusion Criteria:

• Have a prior or planned surgical treatment for obesity
• Have at least one laboratory value suggestive of diabetes during screening
• Use of metformin, or any other glucose-lowering medications
• Have Type 1 Diabetes, latent autoimmune diabetes, been diagnosed with any form of diabetes mellitus except for a prior diagnosis of gestational diabetes mellitus, or history of ketoacidosis or hyperosmolar coma
• Have poorly controlled hypertension

• Have any of the following cardiovascular conditions within 3 months prior to screening:

  • acute myocardial infarction
  • cerebrovascular accident (stroke)
  • unstable angina, or
  • hospitalization due to congestive heart failure
• Have ongoing or a history of frequent intermittent or chronic tachyarrhythmia syndromes
• Have ongoing or a history of bradyarrhythmias other than sinus bradycardia
• Have a history of New York Heart Association (NYHA) Functional Classification III or IV congestive heart failure
• Have a history of symptomatic gallbladder disease within the past 2 years
• Have signs and symptoms of any liver disease
• Have a disease or condition known to cause gastrointestinal malabsorption or a known clinically significant gastric emptying abnormality
• Have a history of acute or chronic pancreatitis
• Have renal impairment, measured as estimated glomerular filtration rate <30 mL/minute/1.73 m2
• Currently taking or have taken medications that may cause significant weight gain or promote weight loss within 3 months prior to screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Bimagrumab Dose 2 + Tirzepatide Placebo; Participants will receive bimagrumab subcutaneously (SC) and tirzepatide placebo SC	Drug: Bimagrumab; Administered SC; Other Names: BYM338; LY3985863; VER201; Drug: Tirzepatide Placebo; Administered SC
Active Comparator: Part A: Bimagrumab Placebo + Tirzepatide Dose 1; Participants will receive bimagrumab placebo SC and tirzepatide SC	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Bimagrumab Placebo; Administered SC
Active Comparator: Part A: Bimagrumab Placebo + Tirzepatide Dose 2; Participants will receive bimagrumab placebo SC and tirzepatide SC	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Bimagrumab Placebo; Administered SC
Experimental: Part A: Bimagrumab Dose 1 + Tirzepatide Dose 1; Participants will receive bimagrumab SC and tirzepatide SC	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Bimagrumab; Administered SC; Other Names: BYM338; LY3985863; VER201
Experimental: Part A: Bimagrumab Dose 1 + Tirzepatide Dose 2; Participants will receive bimagrumab SC and tirzepatide SC	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Bimagrumab; Administered SC; Other Names: BYM338; LY3985863; VER201
Experimental: Part A: Bimagrumab Dose 2 + Tirzepatide Dose 2; Participants will receive bimagrumab SC and tirzepatide SC	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Bimagrumab; Administered SC; Other Names: BYM338; LY3985863; VER201
Placebo Comparator: Part A: Bimagrumab Placebo + Tirzepatide Placebo; Participants will receive bimagrumab placebo SC and tirzepatide placebo SC	Drug: Tirzepatide Placebo; Administered SC; Drug: Bimagrumab Placebo; Administered SC
Experimental: Part B: Bimagrumab Dose 2 (no titration) + Tirzepatide Dose 1; Participants will receive bimagrumab SC and tirzepatide SC	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Bimagrumab; Administered SC; Other Names: BYM338; LY3985863; VER201
Experimental: Part B: Bimagrumab Dose 2 (fast titration) + Tirzepatide Dose 1; Participants will receive bimagrumab SC and tirzepatide SC	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Bimagrumab; Administered SC; Other Names: BYM338; LY3985863; VER201
Experimental: Part B: Bimagrumab Dose 2 (slow titration) + Tirzepatide Dose 1; Participants will receive bimagrumab SC and tirzepatide SC	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Bimagrumab; Administered SC; Other Names: BYM338; LY3985863; VER201
Experimental: Part B: Bimagrumab Dose 1 + Tirzepatide Placebo; Participants will receive bimagrumab SC and tirzepatide placebo SC	Drug: Bimagrumab; Administered SC; Other Names: BYM338; LY3985863; VER201; Drug: Tirzepatide Placebo; Administered SC
Placebo Comparator: Part B: Bimagrumab Placebo + Tirzepatide Placebo; Participants will receive bimagrumab placebo SC and tirzepatide placebo SC	Drug: Tirzepatide Placebo; Administered SC; Drug: Bimagrumab Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Body Weight	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Total Body Fat Mass by Dual-Energy X-Ray Absorptiometry (DXA)	Baseline, Week 24, Week 48
Change from Baseline in Body Weight	Baseline, Week 24, Week 48
Percentage of Participants Achieving ≥5% Body Weight Reduction	Baseline, Week 24, Week 48
Percentage of Participants Achieving ≥10% Body Weight Reduction	Baseline, Week 24, Week 48
Percentage of Participants Achieving ≥15% Body Weight Reduction	Baseline, Week 24, Week 48
Change from Baseline in Waist Circumference	Baseline, Week 24, Week 48
Change from Baseline in Body Mass Index (BMI)	Baseline, Week 24, Week 48
Change from Baseline in Waist-to-Height Ratio (WHtR)	Baseline, Week 24, Week 48
Percent Change from Baseline in Visceral Adipose Tissue (VAT)	Baseline, Week 24, Week 48
Percent Change from Baseline in Total Body Lean Mass by DXA	Baseline, Week 24, 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 Bimagrumab (LY3985863) and Tirzepatide (LY3298176), Alone or in Combination, in Adults With Obesity or Overweight

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 14, 2024
• First Submitted That Met QC Criteria: October 14, 2024
• First Posted (Actual): October 16, 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: Fat; Muscle; Lean
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Platelet Glycoprotein IV Deficiency; 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; bimagrumab
• Other Study ID Numbers: 27265; J4Z-MC-GIDF (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
• product manufactured in and exported from the U.S.: No