LY3305677 for Obesity

No longer recruiting at 44 trial locations

Overseen By Jeffrey A Norton

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Disqualifiers: Diabetes, Cardiovascular conditions, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 58 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of a new treatment, LY3305677 (also known as Mazdutide), for managing weight in adults who are overweight or have obesity. Participants will receive either the treatment or a placebo, and the study will last about 62 weeks. Suitable candidates have a body mass index (BMI) of 27 or higher and do not have diabetes or certain heart and liver conditions. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important weight management research.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants with hypertension should be on a stable antihypertensive regimen for at least 3 months prior to screening, suggesting that you may need to continue certain medications.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medication for high blood pressure, it should be stable for at least 3 months before joining the study.

Is there any evidence suggesting that LY3305677 is likely to be safe for humans?

Research shows that the treatment LY3305677 is generally well-tolerated. In earlier studies, patients taking LY3305677, which affects certain body receptors, handled the medication well. Most reported side effects were mild to moderate, though some people did experience them.

For instance, one study found that even at higher doses, the treatment was safe and helped participants lose weight. This suggests that while some side effects may occur, they are usually not severe, and the benefits may outweigh them for most people.

In summary, human trials have shown LY3305677 to be safe, with side effects that are usually not serious. Participants should always discuss any concerns with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Most treatments for obesity focus on suppressing appetite or blocking fat absorption. However, LY3305677 is unique because it targets the metabolic pathways directly, potentially altering how the body processes and stores energy. This approach could lead to more sustainable weight loss by addressing the root cause of obesity rather than just its symptoms. Researchers are excited about LY3305677 because it offers a novel mechanism of action that could improve effectiveness and provide a new option for patients who don't respond well to existing treatments. Additionally, the subcutaneous delivery method allows for precise dosing and could enhance patient compliance.

What evidence suggests that LY3305677 could be an effective treatment for obesity?

Research shows that LY3305677, also known as mazdutide, may help people with obesity lose weight. Studies have found that mazdutide, a drug activating two specific receptors, led to significant weight loss. In some studies, nearly half of the participants lost at least 10% of their starting weight. The treatment also helped control blood sugar levels, benefiting people with diabetes. These findings suggest LY3305677 could effectively manage weight. Participants in this trial will receive different doses of LY3305677 or a placebo to evaluate its effectiveness and safety. ^{1 2 3 6 7}

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?

This trial is for adults with obesity or overweight, having a BMI of at least 27 kg/m² and one weight-related health issue. Participants must have maintained stable body weight (less than 5% change) in the past three months and agree to follow reproductive safety measures.

Inclusion Criteria

You have a body mass index (BMI) of 27 or higher and at least one weight-related health issue, and your weight has been stable for the past 3 months with no significant gain or loss.

I agree to follow the study's rules about birth control and reproduction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY3305677 or placebo subcutaneously for weight management

58 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3305677
• Placebo

Trial Overview The study tests LY3305677 against a placebo over approximately 62 weeks to see if it's effective and safe for managing weight in obese or overweight adults. It follows a master protocol, meaning it's part of larger research efforts.

How Is the Trial Designed?

Group I: LY3305677 Dose 3 Experimental Treatment 1 Intervention

Participants will receive LY3305677 SC.

Group II: LY3305677 Dose 2 Experimental Treatment 1 Intervention

Participants will receive LY3305677 SC.

Group III: LY3305677 Dose 1 Experimental Treatment 1 Intervention

Participants will receive LY3305677 subcutaneously (SC).

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive LY3305677 matching placebo.

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

Published Research Related to This Trial

Mazdutide, a dual GLP-1 and glucagon receptor agonist, was well tolerated in a phase 1b trial with 24 participants, showing no serious adverse events and only mild to moderate treatment-emergent adverse events.

Participants receiving mazdutide experienced significant weight loss, with a mean reduction of 11.7% at 12 weeks for the 9 mg dose and 9.5% at 16 weeks for the 10 mg dose, compared to much smaller reductions in the placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. Ji, L., Gao, L., Jiang, H., et al.[2022]

Weight loss through diet and exercise can significantly improve glycaemic control in early type 2 diabetes, and pharmacological options like sibutramine and thiazolidinediones are being explored for managing obesity in diabetic patients.

Thiazolidinediones, such as troglitazone, improve insulin resistance but have safety concerns, including severe liver injury, while newer agents like rosiglitazone and pioglitazone show promise with better safety profiles and are effective in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promising new approaches. Reasner, CA.[2011]

In a 72-week phase 3 trial involving 938 adults with obesity and type 2 diabetes, tirzepatide (10 mg and 15 mg) led to significant weight loss, with reductions of -12.8% and -14.7% respectively, compared to only -3.2% with placebo.

The safety profile of tirzepatide was generally favorable, with most adverse events being mild to moderate gastrointestinal issues, and serious adverse events were rare, indicating it is a safe option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Garvey, WT., Frias, JP., Jastreboff, AM., et al.[2023]

LY3437943 is a novel triple agonist that targets three receptors related to metabolism, showing promising results in obese mice by reducing body weight and improving blood sugar control.

In a phase 1 study, LY3437943 demonstrated a safety profile similar to existing treatments and supported once-weekly dosing, with weight loss effects lasting up to 43 days after a single dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Coskun, T., Urva, S., Roell, WC., et al.[2022]

Liraglutide, a diabetes medication, has gained approval in both the US and Europe for obesity treatment and is expected to be widely accepted due to its efficacy.

New research is focusing on activating brown adipose tissue to enhance thermogenesis and developing drugs that mimic gut hormones to achieve results similar to bariatric surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Horizons in the Pharmacotherapy of Obesity. Arch, JR.[2018]

In a 24-week study involving 248 overweight or obese adults in China, mazdutide, a dual GLP-1 and glucagon receptor agonist, resulted in significant weight loss, with reductions of up to 11.3% compared to a 1.0% increase in the placebo group.

Mazdutide was well tolerated across all doses, with common side effects including diarrhea, nausea, and upper respiratory infections, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Ji, L., Jiang, H., Cheng, Z., et al.[2023]

IBI362, a dual agonist for glucagon-like peptide-1 and glucagon receptors, was found to be well tolerated in a phase 1b study with 36 Chinese adults, showing no serious adverse events and only mild gastrointestinal issues as common side effects.

Participants receiving IBI362 experienced significant weight loss, with reductions of approximately 4.81% to 6.40% in body weight over 12 weeks, compared to a minimal change of 0.60% in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study. Ji, L., Jiang, H., An, P., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36247927/

Safety and efficacy of a GLP-1 and glucagon receptor dual ... High-dose mazdutide showed promising 12-week body weight loss, holding great potential for the treatment of moderate-to-severe obesity.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2411528

Once-Weekly Mazdutide in Chinese Adults with Obesity or ... Evidence suggests that incretin-based dual agonist pharmacotherapy is helpful in persons with obesity. Mazdutide, a glucagon-like peptide-1 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589537021003680

IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon ... This study is the first to report the safety, tolerability, pharmacokinetics and primary efficacy of a weekly-dose GLP-1 and glucagon receptor dual agonist in ...

4. investor.innoventbio.com investor.innoventbio.com/media/1228/innovent-clinical-data-update-of-mazdutide-ibi362-2024-ada_20240624_vf.pdf

Mazdutide @ 2024 ADA All above efficacy endpoints are 48-week results of mazdutide 6mg group (treatment-policy estimand), more data presented at 2024 ADA (1856 ...

5. prnewswire.com prnewswire.com/news-releases/innovents-mazdutide-shows-superiority-in-glycemic-control-with-weight-loss-over-semaglutide-in-a-head-to-head-phase-3-clinical-trial-dreams-3-302594633.html

Innovent's Mazdutide Shows Superiority in Glycemic ... The proportion of participants achieving HbA1c < 7.0% and a ≥10% reduction in body weight from baseline was 48.0% in the mazdutide group and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04440345

Study Details | NCT04440345 | Evaluate the Safety, ... The aim of this trial is to investigate Safety, Tolerability, PK and PD for Multiple Doses of IBI362 in Overweight or Obese Male and Female Subjects.

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00421-7/fulltext

Safety and efficacy of a GLP-1 and glucagon receptor dual ... A novel once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist, achieved 12-week body weight loss up to 6.4% at doses up to 6 mg in ...