Bimagrumab + Semaglutide for Obesity

No longer recruiting at 63 trial locations

Overseen By Kiran Dole, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Must not be taking: Antidiabetics, Investigational drugs

Disqualifiers: Diabetes, Chronic infections, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, bimagrumab and semaglutide, to evaluate their effectiveness for weight loss in individuals who are overweight or have obesity, both separately and in combination. The study aims to determine if these treatments can reduce weight safely and effectively. Suitable participants have a body mass index (BMI) of 30 or higher, or a BMI of 27 or higher with conditions like high blood pressure or sleep apnea, and have previously attempted weight loss without success. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant weight loss research.

Do I need to stop my current medications to join the trial?

The trial requires that you stop any medication specifically for obesity at least 30 days before screening. If you are taking medications for other conditions, the protocol does not specify whether you need to stop them, so it's best to discuss this with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both bimagrumab and semaglutide have promising safety records from previous studies. Bimagrumab aids muscle growth and has been tested for up to 48 weeks, proving generally safe and effective in reducing body fat, with no serious side effects reported.

Semaglutide, already approved for other uses, has undergone extensive study. The most common side effects include mild and temporary nausea and diarrhea, which most people tolerate well.

When used together, bimagrumab and semaglutide have demonstrated effectiveness in reducing fat while preserving muscle. This combination is considered safe, with no unexpected side effects reported. These findings suggest that both treatments are likely safe for most people, although individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining bimagrumab and semaglutide for obesity because together, they target both muscle mass and appetite control, which is unique compared to standard weight-loss treatments. Most current options, like diet pills or surgeries, mainly focus on reducing calorie intake or altering digestion. Bimagrumab works by increasing muscle mass, potentially boosting metabolism, while semaglutide helps regulate appetite by mimicking hormones that signal fullness. This dual approach could offer a more comprehensive solution to obesity, addressing both body composition and eating behavior.

What evidence suggests that this trial's treatments could be effective for obesity?

Research shows that bimagrumab can reduce body fat and increase muscle. In earlier studies, participants experienced a noticeable drop in fat and a gain in muscle, which is promising for weight loss. Semaglutide has also been proven to help people lose up to 14.9% of their body weight. In this trial, some participants will receive bimagrumab alone, others will receive semaglutide alone, and some will receive a combination of both. When used together, they have shown even better results in reducing fat and preserving muscle than when used alone. This combination not only focuses on losing fat but also helps improve overall body shape by maintaining muscle. ^{2 3 6 7 8}

Who Is on the Research Team?

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)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

Adults aged 18-80 who are overweight or obese (BMI ≥ 30, or BMI ≥ 27 with related health issues like high blood pressure) can join. They must have tried to lose weight before without success and be willing to follow the study's diet and activity plans. Women able to have children need two negative pregnancy tests and must use an IUD plus a barrier method for contraception.

Inclusion Criteria

A written informed consent must be obtained before any study-related assessments are performed

History of at least one self-reported unsuccessful behavioral effort to lose body weight

Body mass index (BMI) ≥ 30 or BMI ≥ 27 with one or more obesity-associated comorbidities

Exclusion Criteria

I am allergic to some specific drug types or cannot take semaglutide.

I haven't taken any obesity medication in the last 30 days.

I do not have chronic infections like HBV, HCV, or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous bimagrumab and subcutaneous semaglutide according to the dose escalation schedule

48 weeks

Visits at baseline, Weeks 4, 16, 28, 40, 52, and 64

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Extension

Participants may continue to receive bimagrumab during the extension period

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bimagrumab
• Semaglutide

Trial Overview The trial is testing Bimagrumab alone or combined with Semaglutide against a placebo in men and women who are overweight or obese. It aims to find out how effective these treatments are at helping participants lose weight, as well as their safety profiles.

How Is the Trial Designed?

Group I: Placebo + Semaglutide 2.4 mg Experimental Treatment 2 Interventions

Participants received a placebo administered IV at baseline and at weeks 4, 16, 28, and 40, and 2.4 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 12: 1.0 mg Weeks 13 to 16: 1.7 mg Weeks 17 to 48: 2.4 mg.

Group II: Placebo + Semaglutide 1.0 mg Experimental Treatment 2 Interventions

Participants received a placebo administered IV at baseline and at Weeks 4, 16, 28, and 40, and 1 milligram (mg) of semaglutide administered subcutaneously (SC) weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 48: 1.0 mg

Group III: Bimagrumab 30 mg/kg + semaglutide 2.4 mg Experimental Treatment 2 Interventions

Participants received bimagrumab 30 mg/kg administered IV at baseline and at weeks 4, 16, 28 and 40, and 2.4 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 12: 1.0 mg Weeks 13 to 16: 1.7 mg Weeks 17 to 48: 2.4 mg.

Group IV: Bimagrumab 30 mg/kg + Semaglutide 1.0 mg Experimental Treatment 2 Interventions

Participants received bimagrumab 30 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40, and 1 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 48: 1.0 mg

Group V: Bimagrumab 30 mg/kg Experimental Treatment 1 Intervention

Participants received bimagrumab 30 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40.

Group VI: Bimagrumab 10 mg/kg + Semaglutide 2.4 mg Experimental Treatment 2 Interventions

Participants received bimagrumab 10 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40, and 2.4 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 12: 1.0 mg Weeks 13 to 16: 1.7 mg Weeks 17 to 48: 2.4 mg.

Group VII: Bimagrumab 10 mg/kg + Semaglutide 1.0 mg Experimental Treatment 2 Interventions

Participants received bimagrumab 10 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40, and 1 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 48: 1.0 mg.

Group VIII: Bimagrumab 10 mg/kg Experimental Treatment 1 Intervention

Participants received bimagrumab 10 milligrams/kilogram (mg/kg) administered IV at baseline and at weeks 4, 16, 28, and 40 during the core treatment period.

Group IX: Placebo Placebo Group 1 Intervention

Participants received a placebo administered intravenously (IV) at baseline and at weeks 4, 16, 28, and 40 during the core treatment period.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Versanis Bio, Inc.

Industry Sponsor

Trials

2

Recruited

570+

Published Research Related to This Trial

Semaglutide, a GLP-1 receptor agonist, has been shown to effectively lower hemoglobin A1c levels by approximately -1.5% and reduce body weight by about -4.5 kg in phase 3 trials, demonstrating comparable efficacy to dulaglutide.

While semaglutide offers cardiovascular benefits, including a reduced risk of major cardiovascular events, it is associated with an increased risk of retinopathy complications in patients with existing diabetic retinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the Treatment of Type 2 Diabetes Mellitus. Miles, KE., Kerr, JL.[2021]

High-dose once-weekly semaglutide has been shown to significantly reduce weight in patients with obesity or overweight, as demonstrated in four phase 3 clinical trials involving various populations, including those with diabetes.

While gastrointestinal side effects were common, semaglutide was generally well tolerated and also led to improvements in cardiometabolic risk factors, such as waist circumference and blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. Bradley, CL., McMillin, SM., Hwang, AY., et al.[2022]

Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to produce the largest weight loss of any obesity medication, with an average reduction of about 15% of initial body weight over 68 weeks.

In addition to significant weight loss, semaglutide also improves cardiovascular risk factors and physical functioning, making it a promising option for chronic weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. Chao, AM., Tronieri, JS., Amaro, A., et al.[2023]

Semaglutide 2.4mg was found to be the most effective treatment for weight loss in people with obesity, resulting in an average loss of 12.47 kg, and also significantly reduced HbA1c levels compared to placebo.

While semaglutide 2.4mg showed the best efficacy, it also had the highest incidence of adverse events, including hypoglycemia, indicating a trade-off between effectiveness and safety compared to liraglutide treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Liraglutide and Semaglutide on Weight Loss in People with Obesity or Overweight: A Systematic Review. Xie, Z., Yang, S., Deng, W., et al.[2022]

Semaglutide, approved by the FDA on June 4, 2021, is the first new drug for chronic weight management in adults with obesity or overweight since 2014, specifically targeting those with a BMI of 27 or greater and at least one weight-related condition.

This medication is intended to be used alongside a weight management program that includes a reduced-calorie diet and increased physical activity, highlighting its role as part of a comprehensive approach to weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. Mares, AC., Chatterjee, S., Mukherjee, D.[2023]

Subcutaneous semaglutide (Wegovy) has been shown to significantly reduce body weight in overweight and obese individuals, with a dose-dependent effect observed in four Phase 3 trials involving 5000 participants.

While semaglutide resulted in greater weight loss compared to placebo, gastrointestinal side effects were the most common safety concerns, highlighting the need for further studies in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical review of subcutaneous semaglutide for obesity. Phillips, A., Clements, JN.[2022]

Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has been shown to achieve significant and sustained weight loss in individuals with obesity, surpassing results from previous weight-loss medications, and has been approved for use alongside diet and exercise.

Emerging treatments like tirzepatide and cagrilintide are demonstrating even greater weight loss effects than semaglutide, indicating a shift towards more effective 'weight-centric' strategies for managing obesity and related conditions like type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer? Colin, IM., Gérard, KM.[2022]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06901349

NCT06901349 | A Study of Bimagrumab (LY3985863) and ... The main purpose of this study is to see how well and how safely bimagrumab, tirzepatide, and the combination, work in lowering body weight in participants ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2774903

Effect of Bimagrumab vs Placebo on Body Fat Mass Among ... Those who received bimagrumab had a significantly larger decrease in total body fat mas and glycated hemoglobin and increase in lean mass compared with ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33439265/

Effect of Bimagrumab vs Placebo on Body Fat Mass Among ... In this phase 2 randomized clinical trial, ActRII blockade with bimagrumab led to significant loss of FM, gain in LM, and metabolic improvements during 48 ...

4. adameetingnews.org adameetingnews.org/researchers-to-share-weight-loss-results-from-bimagrumab-and-semaglutide-combo/

Researchers to share weight loss results from bimagrumab ... BELIEVE builds on earlier data showing a 20.5% decline in fat mass, a 3.6% increase in lean mass, a 9 cm decline in waist circumference, and 6.5 ...

5. diabetes.org diabetes.org/newsroom/press-releases/new-glp-1-therapies-enhance-quality-weight-loss-improving-muscle-0

New GLP-1 Therapies Enhance Quality of Weight Loss by ... Findings of study demonstrating the effectiveness of combining bimagrumab – a drug designed to combat muscle loss – with a common GLP-1 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05616013

NCT05616013 | Safety and Efficacy of Bimagrumab and ... This study investigates if bimagrumab in addition to semaglutide is able to preserve/increase muscle mass in the presence of weight and/or fat mass loss.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7807292/

Effect of Bimagrumab vs Placebo on Body Fat Mass Among ... This randomized clinical trial evaluates the efficacy and safety of bimagrumab on body composition and glycemic control in adults with type 2 ...

8. trials.lilly.com trials.lilly.com/en-US/trial/546217

A Study to Investigate Weight Management With Bimagrumab ... 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 ...